Studies of Wnt activation in gastric cancer have yielded conflicting results. The goals of this s... more Studies of Wnt activation in gastric cancer have yielded conflicting results. The goals of this study were to determine the frequency of Wnt pathway activation and beta-catenin mutation in these tumors. Three hundred eleven gastric cancers were examined for beta-catenin expression by immunostaining and dissected using laser capture microscopy to obtain DNA from those tumors with nuclear beta-catenin. Exon 3 of beta-catenin was amplified using PCR and sequenced. Ninety gastric cancers (29%) displayed nuclear beta-catenin. DNAs from 73 tumors were amplified and sequenced; 19 (26%) contained mutations in exon 3 of beta-catenin, whereas no mutations were detected in 19 tumors negative for beta-catenin nuclear staining (P < 0.05). Most mutations were adjacent to or abolished known regulatory phosphorylation sites. Mutations in exon 3 of beta-catenin are common in gastric cancer that display nuclear beta-catenin. These results suggest that Wnt pathway activation contributes to carcinogenesis in a subset of gastric adenocarcinomas.
BACKGROUND: beta-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex... more BACKGROUND: beta-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. beta-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered beta-catenin expression in numerous tumor types; however, reports regarding beta-catenin expression in pancreatic cancer have been conflicting.METHODS: beta-Catenin expression was examined in 10 pancreatic cancer cell lines by Western and Northern analysis and by immunofluorescence. Expression was also examined by immunohistochemistry in 57 primary pancreatic cancers and 7 foci of carcinoma-in-situ.RESULTS: Reduced expression of beta-catenin was observed in 4 of 10 pancreatic cancer cell lines. Reduced membranous expression was noted in 32 pancreatic cancers (56%) and correlated with loss of tumor differentiation. Nuclear beta-catenin expression was identified in two tumors (4%). beta-Catenin expression was present in all seven foci of carcinoma-in-situ; however, nuclear expression was predominant in four of the seven cases.CONCLUSIONS: Alterations in beta-catenin expression are common in pancreatic cancer; however, signaling and adhesion functions may be perturbed at different times during tumor progression. Therefore, dysregulation of beta-catenin may contribute to the development and progression of this disease through distinct mechanisms.
Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic du... more Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance. The genomic alterations that commonly occur in pancreatic cancer include activation of KRAS2 and inactivation of p53 and SMAD4 (refs 2-4). So far, however, it has been challenging to target these pathways therapeutically; thus the search for other key mediators of pancreatic cancer growth remains an important endeavour. Here we show that the stem cell determinant Musashi (Msi) is a critical element of pancreatic cancer progression both in genetic models and in patient-derived xenografts. Specifically, we developed Msi reporter mice that allowed image-based tracking of stem cell signals within cancers, revealing that Msi expression rises as pancreatic intraepithelial neoplasia progresses to adenocarcinoma, and that Msi-expressing cells are key drivers of pancreat...
The RON tyrosine kinase receptor is under investigation as a novel target in pancreatic cancer. W... more The RON tyrosine kinase receptor is under investigation as a novel target in pancreatic cancer. While RON mutations are uncommon, RON isoforms are produced in cancer cells via a variety of mechanisms. In this study we sought to; 1) characterize RON isoform expression in pancreatic cancer, 2) investigate mechanisms that regulate isoform expression, and 3) determine how various isoforms effect gene expression, oncogenic phenotypes and responses to RON directed therapies. We quantified RON transcripts in human pancreatic cancer and found expression levels 2500 fold that of normal pancreas with RON isoform expression comprising nearly 50% of total transcript. RNA seq studies revealed that the short form (sfRON) and P5P6 isoforms which have ligand independent activity, induce markedly different patterns of gene expression than wild type RON. We found that transcription of RON isoforms is regulated by promoter hypermethylation as the DNA demethylating agent 5-aza-2'-deoxycytidine decreased all RON transcripts in a subset of pancreatic cancer cell lines. The viability of sfRON-expressing HPDE cells was reduced by a RON specific small molecule inhibitor, while a therapeutic monoclonal antibody had no demonstrable effects. In summary, RON isoforms may comprise half of total RON transcript in human pancreatic cancer and their expression is regulated at least in part by promoter hypermethylation. RON isoforms activate distinct patterns of gene expression, have transforming activity and differential responses to RON directed therapies. These findings further our understanding of RON biology in pancreatic cancer and have implications for therapeutic strategies to target RON activity.
Archives of Pathology Laboratory Medicine, Feb 1, 2003
The patient was a 43-year-old African American woman who complained of recent development of a ma... more The patient was a 43-year-old African American woman who complained of recent development of a mass on the lateral aspect of the left arm. The patient initially thought the mass was related to an insect bite, but when it persisted for several weeks, she sought evaluation. The ...
Although consensus statements support the preoperative treatment of borderline resectable pancrea... more Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50-76 years]; 55% female)...
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low five-year survival ra... more Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low five-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates anti-tumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8+ T cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacological inhibition of PI3Kγ represents a new therapeutic modality for this devasta...
Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally... more Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of tumor penetrating peptides identified using phage display are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA). We expressed the peptide, uCendR (RPARSGR↓SAGGSVA, ↓ shows cleavage site), on phage or coated it onto silver nanoparticles and showed that it is cleaved by uPA, and that the cleavage triggers binding to recombinant NRP-1 and to NPR-1-expressing cells. Upon systemic administration to mice bearing uPA-overexpressing breast tumors, FAM-labeled uCendR peptide and uCendR-coated nanoparticles preferentially accumulated in tumor tissue. We also show that uCendR phage internalization into cultured cancer cells and its penetration in explants of murine tumors and clinical tumor explants can be potentiated by combining the uCendR peptide with tumor-homing module, CRGDC. Our work demonstrates the feasibility of designing tumor-penetrating peptides that are activated by a specific tumor protease. As upregulation of protease expression is one of the hallmarks of cancer, and numerous tumor proteases have substrate specificities compatible with proteolytic unmasking of cryptic CendR motifs, the strategy described here may provide a generic approach for designing proteolytically-actuated peptides for tumor-penetrative payload delivery.
Background: ß-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to... more Background: ß-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. ß-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered ß-catenin expression in numerous tumor types; however, reports regarding ß-catenin expression in pancreatic
The RON receptor is increasingly over-expressed during pancreatic cancer progression and has been... more The RON receptor is increasingly over-expressed during pancreatic cancer progression and has been implicated as a mediator of KRAS oncogene addiction. It remains unclear if RON promotes disease progression or simply represents an epiphenomenon.To address this, we generated a transgenic mouse which over-expressed wt-RON in a pancreas-specific manner using Pdx-1, the identical promoter used to drive cre expression in the Kras-LSLGD12/Pdx-1-cre (KC) strain that develops pancreatic duct neoplasia. RON over-expression was verified via Western and IHC. Pdx-1/RON mice were crossed with LSL-KRASG12D mice to yield mice (RK), then bred to Pdx-1-Cre mice to combine RON over-expression in the presence of oncogenic KRAS (RCK). RCK mice were aged and sacrificed at various time points and histology compared to KC controls.Pdx-1-RON mice developed no pancreatic phenotype prior to 12 months. At 18 months, one of 4 animals developed primary pancreatic adenocarcinoma with lung metastasis. RON overexpression in KRAS mutant mice (RCK) led to accelerated PanIN progression compared to KC (p<0.05). In RCK, PanIN's were visible at 6 weeks, with invasive carcinoma detectable at 6 months compared to KC mice (average latency >1yr). Metastatic disease was visible in RCK mice at 9 months.RON overexpression alone results in pancreatic cancer at long latency. In the presence of KRAS mutation, RON overexpression markedly accelerates PanIN progression to primary and metastatic pancreatic duct cancer. This data supports a role for RON in pancreatic carcinogenesis and this model may prove useful for investigations regarding the role of the RON receptor in pancreatic cancer biology.
BACKGROUND: beta-Catenin is a component of the E-cadherin/catenin adhesion complex that maintains... more BACKGROUND: beta-Catenin is a component of the E-cadherin/catenin adhesion complex that maintains epithelial cell integrity. We have previously observed decreased beta-catenin expression in both human pancreatic cancer cell lines and primary tumors. To determine the significance of this finding with respect to pancreatic carcinogenesis, this study evaluated the effects of restoring expression of beta-catenin with and without E-cadherin in pancreatic cancer cells.METHODS: MiaPaca-2 cells were stably transfected with full-length cDNAs for beta-catenin, E-cadherin, or a mutated E-cadherin lacking the beta-catenin-binding domain. Doubly transfected cell clones containing beta-catenin and either E-cadherin or deleted E-cadherin were also selected. Assays for cell adhesion, cell cycle profile, motility, and apoptosis were performed.RESULTS: Cell clones expressing beta-catenin alone or beta-catenin and deleted E-cadherin did not differ significantly from the parental cell lines in any of the assays performed. In contrast, MiaPaca-2 cell clones expressing both beta-catenin and E-cadherin showed tight adhesion, decreased cell growth, and a significantly increased apoptotic index as compared to the parental line or singly transfected clones.CONCLUSIONS: MiaPaca-2 cells undergo apoptosis at a significantly increased rate after restoration of the E-cadherin/beta-catenin adhesion complex. This increase in apoptosis is dependent on the ability of E-cadherin to bind beta-catenin. Loss of beta-catenin expression may therefore provide pancreatic cancer cells with a growth advantage that contributes to tumor progression.
Page 1. Clinical Colorectal Cancer August 2003 113 Introduction Approximately 250,000 new patie... more Page 1. Clinical Colorectal Cancer August 2003 113 Introduction Approximately 250,000 new patients were diagnosed with gastrointestinal cancers in the United States in 2002, with ap-proximately 132,000 deaths resulting ...
Studies of Wnt activation in gastric cancer have yielded conflicting results. The goals of this s... more Studies of Wnt activation in gastric cancer have yielded conflicting results. The goals of this study were to determine the frequency of Wnt pathway activation and beta-catenin mutation in these tumors. Three hundred eleven gastric cancers were examined for beta-catenin expression by immunostaining and dissected using laser capture microscopy to obtain DNA from those tumors with nuclear beta-catenin. Exon 3 of beta-catenin was amplified using PCR and sequenced. Ninety gastric cancers (29%) displayed nuclear beta-catenin. DNAs from 73 tumors were amplified and sequenced; 19 (26%) contained mutations in exon 3 of beta-catenin, whereas no mutations were detected in 19 tumors negative for beta-catenin nuclear staining (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Most mutations were adjacent to or abolished known regulatory phosphorylation sites. Mutations in exon 3 of beta-catenin are common in gastric cancer that display nuclear beta-catenin. These results suggest that Wnt pathway activation contributes to carcinogenesis in a subset of gastric adenocarcinomas.
BACKGROUND: beta-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex... more BACKGROUND: beta-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. beta-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered beta-catenin expression in numerous tumor types; however, reports regarding beta-catenin expression in pancreatic cancer have been conflicting.METHODS: beta-Catenin expression was examined in 10 pancreatic cancer cell lines by Western and Northern analysis and by immunofluorescence. Expression was also examined by immunohistochemistry in 57 primary pancreatic cancers and 7 foci of carcinoma-in-situ.RESULTS: Reduced expression of beta-catenin was observed in 4 of 10 pancreatic cancer cell lines. Reduced membranous expression was noted in 32 pancreatic cancers (56%) and correlated with loss of tumor differentiation. Nuclear beta-catenin expression was identified in two tumors (4%). beta-Catenin expression was present in all seven foci of carcinoma-in-situ; however, nuclear expression was predominant in four of the seven cases.CONCLUSIONS: Alterations in beta-catenin expression are common in pancreatic cancer; however, signaling and adhesion functions may be perturbed at different times during tumor progression. Therefore, dysregulation of beta-catenin may contribute to the development and progression of this disease through distinct mechanisms.
Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic du... more Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance. The genomic alterations that commonly occur in pancreatic cancer include activation of KRAS2 and inactivation of p53 and SMAD4 (refs 2-4). So far, however, it has been challenging to target these pathways therapeutically; thus the search for other key mediators of pancreatic cancer growth remains an important endeavour. Here we show that the stem cell determinant Musashi (Msi) is a critical element of pancreatic cancer progression both in genetic models and in patient-derived xenografts. Specifically, we developed Msi reporter mice that allowed image-based tracking of stem cell signals within cancers, revealing that Msi expression rises as pancreatic intraepithelial neoplasia progresses to adenocarcinoma, and that Msi-expressing cells are key drivers of pancreat...
The RON tyrosine kinase receptor is under investigation as a novel target in pancreatic cancer. W... more The RON tyrosine kinase receptor is under investigation as a novel target in pancreatic cancer. While RON mutations are uncommon, RON isoforms are produced in cancer cells via a variety of mechanisms. In this study we sought to; 1) characterize RON isoform expression in pancreatic cancer, 2) investigate mechanisms that regulate isoform expression, and 3) determine how various isoforms effect gene expression, oncogenic phenotypes and responses to RON directed therapies. We quantified RON transcripts in human pancreatic cancer and found expression levels 2500 fold that of normal pancreas with RON isoform expression comprising nearly 50% of total transcript. RNA seq studies revealed that the short form (sfRON) and P5P6 isoforms which have ligand independent activity, induce markedly different patterns of gene expression than wild type RON. We found that transcription of RON isoforms is regulated by promoter hypermethylation as the DNA demethylating agent 5-aza-2&amp;amp;amp;amp;#39;-deoxycytidine decreased all RON transcripts in a subset of pancreatic cancer cell lines. The viability of sfRON-expressing HPDE cells was reduced by a RON specific small molecule inhibitor, while a therapeutic monoclonal antibody had no demonstrable effects. In summary, RON isoforms may comprise half of total RON transcript in human pancreatic cancer and their expression is regulated at least in part by promoter hypermethylation. RON isoforms activate distinct patterns of gene expression, have transforming activity and differential responses to RON directed therapies. These findings further our understanding of RON biology in pancreatic cancer and have implications for therapeutic strategies to target RON activity.
Archives of Pathology Laboratory Medicine, Feb 1, 2003
The patient was a 43-year-old African American woman who complained of recent development of a ma... more The patient was a 43-year-old African American woman who complained of recent development of a mass on the lateral aspect of the left arm. The patient initially thought the mass was related to an insect bite, but when it persisted for several weeks, she sought evaluation. The ...
Although consensus statements support the preoperative treatment of borderline resectable pancrea... more Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50-76 years]; 55% female)...
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low five-year survival ra... more Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low five-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates anti-tumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8+ T cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacological inhibition of PI3Kγ represents a new therapeutic modality for this devasta...
Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally... more Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of tumor penetrating peptides identified using phage display are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA). We expressed the peptide, uCendR (RPARSGR↓SAGGSVA, ↓ shows cleavage site), on phage or coated it onto silver nanoparticles and showed that it is cleaved by uPA, and that the cleavage triggers binding to recombinant NRP-1 and to NPR-1-expressing cells. Upon systemic administration to mice bearing uPA-overexpressing breast tumors, FAM-labeled uCendR peptide and uCendR-coated nanoparticles preferentially accumulated in tumor tissue. We also show that uCendR phage internalization into cultured cancer cells and its penetration in explants of murine tumors and clinical tumor explants can be potentiated by combining the uCendR peptide with tumor-homing module, CRGDC. Our work demonstrates the feasibility of designing tumor-penetrating peptides that are activated by a specific tumor protease. As upregulation of protease expression is one of the hallmarks of cancer, and numerous tumor proteases have substrate specificities compatible with proteolytic unmasking of cryptic CendR motifs, the strategy described here may provide a generic approach for designing proteolytically-actuated peptides for tumor-penetrative payload delivery.
Background: ß-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to... more Background: ß-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. ß-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered ß-catenin expression in numerous tumor types; however, reports regarding ß-catenin expression in pancreatic
The RON receptor is increasingly over-expressed during pancreatic cancer progression and has been... more The RON receptor is increasingly over-expressed during pancreatic cancer progression and has been implicated as a mediator of KRAS oncogene addiction. It remains unclear if RON promotes disease progression or simply represents an epiphenomenon.To address this, we generated a transgenic mouse which over-expressed wt-RON in a pancreas-specific manner using Pdx-1, the identical promoter used to drive cre expression in the Kras-LSLGD12/Pdx-1-cre (KC) strain that develops pancreatic duct neoplasia. RON over-expression was verified via Western and IHC. Pdx-1/RON mice were crossed with LSL-KRASG12D mice to yield mice (RK), then bred to Pdx-1-Cre mice to combine RON over-expression in the presence of oncogenic KRAS (RCK). RCK mice were aged and sacrificed at various time points and histology compared to KC controls.Pdx-1-RON mice developed no pancreatic phenotype prior to 12 months. At 18 months, one of 4 animals developed primary pancreatic adenocarcinoma with lung metastasis. RON overexpression in KRAS mutant mice (RCK) led to accelerated PanIN progression compared to KC (p<0.05). In RCK, PanIN's were visible at 6 weeks, with invasive carcinoma detectable at 6 months compared to KC mice (average latency >1yr). Metastatic disease was visible in RCK mice at 9 months.RON overexpression alone results in pancreatic cancer at long latency. In the presence of KRAS mutation, RON overexpression markedly accelerates PanIN progression to primary and metastatic pancreatic duct cancer. This data supports a role for RON in pancreatic carcinogenesis and this model may prove useful for investigations regarding the role of the RON receptor in pancreatic cancer biology.
BACKGROUND: beta-Catenin is a component of the E-cadherin/catenin adhesion complex that maintains... more BACKGROUND: beta-Catenin is a component of the E-cadherin/catenin adhesion complex that maintains epithelial cell integrity. We have previously observed decreased beta-catenin expression in both human pancreatic cancer cell lines and primary tumors. To determine the significance of this finding with respect to pancreatic carcinogenesis, this study evaluated the effects of restoring expression of beta-catenin with and without E-cadherin in pancreatic cancer cells.METHODS: MiaPaca-2 cells were stably transfected with full-length cDNAs for beta-catenin, E-cadherin, or a mutated E-cadherin lacking the beta-catenin-binding domain. Doubly transfected cell clones containing beta-catenin and either E-cadherin or deleted E-cadherin were also selected. Assays for cell adhesion, cell cycle profile, motility, and apoptosis were performed.RESULTS: Cell clones expressing beta-catenin alone or beta-catenin and deleted E-cadherin did not differ significantly from the parental cell lines in any of the assays performed. In contrast, MiaPaca-2 cell clones expressing both beta-catenin and E-cadherin showed tight adhesion, decreased cell growth, and a significantly increased apoptotic index as compared to the parental line or singly transfected clones.CONCLUSIONS: MiaPaca-2 cells undergo apoptosis at a significantly increased rate after restoration of the E-cadherin/beta-catenin adhesion complex. This increase in apoptosis is dependent on the ability of E-cadherin to bind beta-catenin. Loss of beta-catenin expression may therefore provide pancreatic cancer cells with a growth advantage that contributes to tumor progression.
Page 1. Clinical Colorectal Cancer August 2003 113 Introduction Approximately 250,000 new patie... more Page 1. Clinical Colorectal Cancer August 2003 113 Introduction Approximately 250,000 new patients were diagnosed with gastrointestinal cancers in the United States in 2002, with ap-proximately 132,000 deaths resulting ...
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