Abstract 2454: Ampk and hdac pathways and regulation rassf1c gene expression

Introduction: We have previously shown that RASSF1C promotes cell proliferation, migration and attenuates apoptosis in cancer cells. We have also shown that RASSF1C is significantly up-regulated in breast and lung cancer tissues compared to normal tissues. Together these demonstrate that RASSF1C, is not a tumor suppressor like RASSF1A, but instead appears to function as an oncoprotein.Currently nothing is known about the upstream signaling cascades involved in regulating RASSF1C gene expression and thus we performed transcriptome PCR array study to identify chemicals inhibitors that modulate(s) RASSF1C expression.Method: A transcriptome PCR array was obtained from Qiagen. It consisted of cDNA from breast cancer cell line MCF7 cells treated with 90 different chemical inhibitors that regulate various signaling pathways. The array was screened with RASSF1C gene specific primers. Data analysis was performed by importing the Ct values obtained into data analysis software.Results: The PCR array screen identified several chemical reagents that appear to up-regulate and several that seem to down-regulate RASSF1C expression by ≥ 1.5 fold. The two most notable reagents are Dorsopmorhin (AMPK inhibitor) which up-regulates RASSF1C expression by 2.8 fold and Trichostatin A (HDAC inhibitor) which down regulates RASSF1C expression by 2 fold. We are in process of confirming the effect of these inhibitors in a panel of breast and lung cancer cells.Conclusion: The findings are novel and suggest that inhibition of AMPK pathway induces RASSF1C expression while inhibition of HDAC pathway suppresses RASSF1C gene expression. We should note that Trichostatin A has been shown to activate AMPK, inhibits HDAC, arrests cell growth, and induces apoptosis in human cancers. Our findings provide a potential mechanism for regulating RASSF1C gene expression through the modulation of AMPK and HDAC pathways.Citation Format: Yousef G. Amaar, Mark E. Reeves, Matthew Firek. Ampk and hdac pathways and regulation rassf1c gene expression. [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 2454. doi:10.1158/1538-7445.AM2014-2454