Ccn6 Downregulation In Invasive Breast Carcinomas: In Situ Characterization Of Changes In Emt Proteins And Metastatic Disease

Background: The recognized heterogeneity of invasive breast carcinomas is a result of intrinsic characteristics of the tumor cells and their interaction with the microenvironment. CCN6, an extracellular matricellular protein involved in cell communication and epithelial-stromal interactions has a tumor suppressor role in breast cancer. CCN6 downregulation in benign breast cells induces an epithelial to mesenchymal transition marked by downregulation of E-cadherin and increased levels of the transcriptional regulators ZEB1 and Snai1. However, the relevance of these studies to human breast cancer needs further investigation. We hypothesized that CCN6 mRNA and protein levels in samples of breast cancer patients may be associated with metastasis and features of EMT. Methods: Forty clinical samples of invasive carcinoma and surrounding normal breast, frozen at the time of operation were collected. We extracted mRNA and protein from each sample and performed real time RT-PCR and Western blots for CCN6, respectively. All frozen samples were immunostained with antibodies against E-cadherin (BD Biosciences, 1:4000), ZEB1 (Santa Cruz Biotechnology, 1:400) and Snai1(Cell Signaling, 1:800). E-cadherin was analyzed as aberrant or normal. ZEB1 and Snai1 proteins were scored as positive or negative, either in the cancer or stromal cells. Results: Of the 40 frozen samples of breast cancer, 23 had high quality RNA and protein for further study. CCN6 mRNA and protein were both decreased in 18/23 (78%). Five of 23 (22%) samples exhibited normal or high expression. Low CCN6 was associated with the presence of distant metastasis. Four of 18 (22%) invasive carcinomas with low CCN6 had distant metastasis compared to none of the normal CCN6 expressing tumors (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 37. doi:1538-7445.AM2012-37