Kai Lee Yap
University of Chicago, Medicine, Post-Doc
Research Interests:
Research Interests: Cancer, Cell Cycle, Autophagy, Ovarian Cancer, Apoptosis, and 17 moreGene expression, Nucleus Accumbens, RNA interference, Cell line, Adenosine, Humans, Epidermal Growth Factor/ErbB receptors, Female, Drug Resistance, Oncogene, Clinical Sciences, Cisplatin, Chloroquine, Gene Family, Cell Survival, Functional Status, and Protein Transport
Research Interests:
Research Interests:
Research Interests: Cancer, Transcription Factors, Humans, Mice, Female, and 3 moreAnimals, HeLa cells, and Transfection
Research Interests: Oncology and Y chromosome
Research Interests:
Research Interests: Engineering, Physics, Chemistry, Biology, Proteomics, and 16 moreOvarian Cancer, Apoptosis, Medicine, Multidisciplinary, Humans, Female, Drug Resistance, Tandem Mass Spectrometry, PLoS one, Liquid Chromatography / Electrospray Ionization Mass Spectrometry, Chromatin Immunoprecipitation, DNA binding, Ovarian Carcinoma, Antineoplastic Agents, Enzyme Linked Immunosorbent Assay, and Carboplatin
Nucleus accumbens-1 (Nac1 or NAC-1) belongs to the BTB/POZ transcription factor family and is a novel protein that potentially participates in self-renewal and pluripotency in embryonic stem cells. In human cancer, NAC-1 is upregulated in... more
Nucleus accumbens-1 (Nac1 or NAC-1) belongs to the BTB/POZ transcription factor family and is a novel protein that potentially participates in self-renewal and pluripotency in embryonic stem cells. In human cancer, NAC-1 is upregulated in several types of neoplasms, but particularly in recurrent chemoresistant ovarian carcinomas, suggesting a biological role for NAC-1 in the development of drug resistance in ovarian cancer. We have assessed this possibility and demonstrated a correlation between NAC-1 expression and ex vivo paclitaxel resistance in ovarian serous carcinoma tissues and cell lines. We found that expression of Gadd45gamma-interacting protein 1 (Gadd45gip1), a downstream target negatively regulated by NAC-1, was reduced in paclitaxel-resistant cells. Ectopic expression of NAC-1 or knockdown of Gadd45gip1 conferred paclitaxel resistance, while NAC-1 knockdown or ectopic expression of Gadd45gip1 increased paclitaxel sensitivity. Furthermore, silencing NAC-1 expression or disrupting NAC-1 homodimerization by a dominant negative NAC-1 protein that contained only the BTB/POZ domain induced expression of Gadd45gamma which interacted with Gadd45gip1. Reducing Gadd45gamma expression by shRNAs partially enhanced paclitaxel resistance. Thus, this study provides new evidence that NAC-1 upregulation and homodimerization contribute to tumor recurrence by equipping ovarian cancer cells with the paclitaxel-resistant phenotype through negative regulation of the Gadd45 pathway.