Abstract 2954: The transient receptor potential V6 (TRPV6) calcium channel in breast cancer cell lines and clinical breast cancer tissues

Abstract

Abstract TRPV6 is an important calcium channel, which is highly selective for Ca2+ and has high basal activity. In prostate tumors TRPV6 over-expression is linked to enhanced invasiveness and proliferation. While some studies have demonstrated that TRPV6 is over-expressed in clinical breast cancer samples and studies from our laboratory have shown that TRPV6 mRNA is up-regulated in a sub-set of breast cancer cell lines, a link between TRPV6 expression and breast cancer aggressiveness has not been demonstrated. Furthermore, the mechanism for the over-expression of TRPV6 in breast cancer is unknown. To explore TRPV6 gene amplification as a possible mechanism for over-expression, we used a real-time PCR copy number assay and identified a sub-set of breast cancer cells lines that exhibited increased TRPV6 gene copy number. To assess the clinical relevance of this finding, we initially used a high throughout, clinically driven approach to examine TRPV6 gene amplification in breast tumors. Our findings showed that the mechanism of TRPV6 over-expression is due to, at least in part, gene amplification and that gene amplification may be pronounced in breast cancer subtypes with a poor prognosis. In clinical breast tumor samples, microarray based comparative genomic hybridization (aCGH) showed that the TRPV6 gene region (7q34) is gained in 0/16 invasive lobular carcinomas and in 11/35 high grade invasive ductal carcinomas. When stratified by estrogen receptor status, 7/13 estrogen receptor negative, high grade invasive ductal carcinomas harbored a gain in this region. To determine whether the copy number increase observed at the gene region 7q34 specifically corresponded with amplification of the TRPV6 gene, we performed chromogenic in situ hybridization (CISH) using a probe specific for the TRPV6 gene and a breast cancer tissue microarray. Our findings suggest that a sub-set of breast cancers may be characterized by TRPV6 gene amplification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2954. doi:10.1158/1538-7445.AM2011-2954