Abstract A73: In vivo evidence of TIMPv as a potential target of CD146-signaling inhibiting breast tumor invasion

Abstract

Abstract CD146, also known as melanoma cell adhesion molecule (Mel-CAM, MCAM) or MUC18, was initially identified as a marker of melanoma progression and a promoter of melanoma and prostate cancer (PC) metastasis. In contrast, CD146 appears to play a tumor suppression role in breast cancer (BC). Here, we applied microarray gene expression profiling analysis, using a tetracycline (tet On)-inducible system of CD146 in the MDA-MB-231 BC cell line, and we identified TIMPv (a variant of Tissue Inhibitor of Metalloproteinases), showing a 7 fold increase, as a potential CD146-downstream signaling transcriptional target; this was confirmed in vitro by both time-course western blotting and RT-PCR. Furthermore, breast tumor tissues from both Omani patients and patients from New Orleans area in Louisiana, were examined by immunohistochemistry for the expression of CD146 and TIMPv. Strikingly, the results revealed that the expression levels of both CD146 and its downstream target TIMPv showed parallel inhibition patterns in BC progression, with high expression in normal and benign but low or no expression in malignant and metastatic breast tumor tissue. These findings support the hypothesis that the expression of both, CD146 and its downstream target TIMPv, is lost during BC progression and metastasis. Ongoing studies in our laboratory aim to shed light on the molecular components linking CD146 to the activation of TIMPv transcription. Citation Format: Allal Ouhtit, Zakariya Y. Abd Elmageed, Sunil Bhat, Pravrutha Raman, Suad H. Al-Jardani, Ishita Gupta, Somya Shanmuganathan, Hamad Al-Riyami. In vivo evidence of TIMPv as a potential target of CD146-signaling inhibiting breast tumor invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A73.