Abstract 2330: Transcription factor MAZ promotes cell growth and aggressive behavior of human pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cancer in the United States and the eighth worldwide. PDAC is most aggressive type of cancer that spreads rapidly and is seldom detected in its early stages as signs and symptoms may not appear until pancreatic cancer is quite advanced. MAZ (Myc-associated zinc-finger protein) or SAF1 (Serum amyloid A activating factor 1) gene is a member of multiple Cys 2 -His 2 -type zinc finger proteins that are activated in response to various inflammatory signals and may act as a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression has been shown to be related to the development and progression of various cancers like prostate cancer, breast cancer and pancreatic cancer. However, mode of action of MAZ in carcinogenesis is unclear. We found that MAZ mRNA and protein levels were markedly elevated in pancreatic adenocarcinoma tissue samples as compared to adjacent normal tissues and the expression profile was increased as the disease progressed. Similarly, MAZ mRNA and protein levels were increased several folds in aggressive pancreatic cancer cell lines as compared to non-transformed pancreatic cancer cell lines. Functional analysis demonstrates that siRNA-based depletion of MAZ significantly inhibits in vitro cellular growth, colony formation, anchorage independent growth and invasion in pancreatic cancer cells. Mechanistically, MAZ regulates BIRC5, a pancreatic cancer promoting gene, to possibly exert its pathobiological function. Moreover, we found that CCN1/Cyr61 is an upstream regulator of MAZ. Collectively, these findings indicate that MAZ is a downstream target of CCN1 and plays an important role in pancreatic cancer progression and differentiation. Thus, MAZ could be an ideal target for PDAC management. [This work is supported by VA Merit Award Grant (SB/SKB)] Citation Format: Gargi Maity, Sandipto Sarkar, Kakali Dhar, Gopal Dhar, Inamul Haque, Sushanta K. Banerjee, Snigdha Banerjee. Transcription factor MAZ promotes cell growth and aggressive behavior of human pancreatic cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2330. doi:10.1158/1538-7445.AM2014-2330