Abstract 2339: Transcriptional basis for loss of cellular differentiation in colon cancer

Abstract

Abstract Background: Colon cancer is a leading cause of cancer related death. Colon cancer arises due to uncontrolled cell proliferation, failure of cells to undergo apoptosis and loss of cellular differentiation. While the pathways which drive the uncontrolled proliferation of colon cancer cells are relatively well understood, the mechanistic basis for loss of cell differentiation is less well characterized. The aim of this study was to identify novel transcription factors that regulate the differentiation status of colon cancer cells. Methods: Affymetrix microarrays were used to identify transcription factors which are significantly differentially expressed between well differentiated and poorly differentiated colon cancer cell lines. Differential gene expression was confirmed by q-RT-PCR in 40 colon cancer cell lines. The well differentiated colon cancer cell line SW948 was transfected with siRNAs using lipofectamine. Results: Microarray analysis of well and poorly differentiated colon cancer cell lines identified the EHF transcription factor to be significantly downregulated in expression in poorly differentiated cell lines. Q-RT-PCR analysis demonstrated that while both EHF variants were expressed in a panel of 40 colon cancer cells, variant 2 was the isoform differentially expressed between well and poorly differentiated cell lines. Basal expression of EHF correlated significantly with expression of the differentiation markers villin and KRT20 across the 40 cell line panel. Knockdown of EHF in the well differentiated colon cancer cell line SW948, reduced expression of villin and KRT20 by 82% and 64% respectively. Knockdown of EHF also reduces expression of Cdx1 suggesting it may be act upstream of this known differentiation regulator. Conclusion: This study identifies the transcription factor EHF as a novel regulator of cell differentiation in colon cancer. Citation Format: Ian Y. Luk, Hoanh Tran, Janson WT Tse, Anderly C. Chueh, Fiona Chionh, Nicholas J. Clemons, John M. Mariadason. Transcriptional basis for loss of cellular differentiation in colon cancer. [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 2339. doi:10.1158/1538-7445.AM2014-2339