Abstract P3-04-02: Invasive lobular carcinoma cell lines utilize WNT4 signaling to mediate estrogen-induced growth

Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer representing 10-15% of newly diagnosed breast tumors. Over 90% of ILC are estrogen receptor (ER)-positive, however, endocrine response and estrogen signaling are not well understood in ILC. Retrospective analyses suggest that ILC patients treated with endocrine therapy have poorer outcomes than invasive ductal carcinoma (IDC) patients, and that ILC patients may not benefit from adjuvant tamoxifen. Based on these observations, we hypothesize that ER regulates unique signaling pathways in ILC cells that control growth and endocrine response.To identify putative targets that regulate endocrine response in ILC, we assessed genome-wide ER-mediated gene expression and ER genomic binding in the ILC cell lines MDA MB 134VI (MM134) and SUM44PE (SUM44). Among ILC-specific estrogen-regulated genes, the most strongly induced was the secreted ligand WNT4. Additionally, we identified an ILC-specific ER binding site (ERBS) at WNT4, suggesting that WNT4 is directly controlled by ER in ILC cells. Direct ER-regulation of WNT4 is in contrast to control of WNT4 by progesterone receptor (PR) during mammary gland development; however, further ER ChIP experiments suggest that ILC cells place WNT4 under ER control via unique use of the WNT4 ERBS. Thus, ILC cells may hijack a tightly regulated developmental program to drive estrogen-regulated cell phenotypes.Based on the role of WNT4 in mammary gland growth and expansion, we ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research