Abstract 3084: Chfr in breast cancer development

Abstract

Abstract Breast cancer is a common malignancy and is the most frequently diagnosed cancer in USA. It can be developed when genes that control the cell cycle and genomic stability are aberrantly expressed or non-functional. Where CHFR encodes an ubiquitin ligase that reportedly delays mitosis in response to microtubule-targeting drugs (i.e. nocodazoles and taxanes). CHFR (Checkpoint with FHA and Ring Finger) is hypothesized to mediate a delay in cell cycle progression, early in mitosis, in response to microtubule stress, independent of the spindle assembly checkpoint. As a potential regulator of cell cycle progression, CHFR naturally becomes an interesting target for understanding cancer cells. Low or moderate CHFR mRNA expression has been already reported in many cancers including breast cancer with some relevance to tumor suppressor activities. In this study we analyzed the expression profiles of CHFR in different breast cancer cell lines at mRNA and protein levels using real-time PCR and immuno-Western blot analysis. We also analyzed its expression in various breast tissue samples using immunohistochemistry. We found CHFR mRNA was significantly higher in BT474 and MCF-7 cells as compared to MDA-MB-231 cells. Two isoforms (i.e.,) of CHFR protein were detected in these cells. High molecular weight (∼89kD) isoform was markedly elevated in MDA-MB-231 cells as compared to MCF-7 cells while low molecular weight (∼52kD) isoform markedly reduced in MDA-MB-231 cells. Moreover, in normal breast sample CHFR expression is nuclear while in adenocarcinoma samples CHFR was prominent expression in cytoplasmic. Finally, we found that high molecular weight CHFR isoform expression can be regulated negatively by CCN5/WISP-2, an anti-invasive gene. Collectively, these studies suggest that CHFR may play dual roles in the genesis of breast cancer and possibly, the high molecular weight isoform may play critical role in progression of breast cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3084.