p53 mutant mediates CXCR7 expression and function in breast cancer progression

• Main Authors: Shyuan-Ling Lin, 林瑄翎
• Other Authors: 謝佳宏
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/43999812932189422991

碩士 === 中國醫藥大學 === 基礎醫學研究所碩士班 === 99 === CXCR7 was identified as a novel, alternate receptor for CXCL12 that promotes tumor growth and metastasis in breast cancer and other malignancies. However, the expression and function of CXCR7 in tumor progression is controversial. This issue may be due to complex genetic alterations. Here, we show that two human breast tumor cell lines (MCF-7 and MDA-MB-231) have different expression levels of CXCR7. The poorly invasive MCF-7 cell line was up-regulation of CXCR7, whereas the highly invasive MDA-MB-231 cell line was down-regulation of CXCR7. The p53 levels are associated with CXCR7 expression. The p53 gain-of-function mutation in MDA-MB-231 cells suppressed CXCR7 expression via up-regulation of hypermethylated in cancer 1 (HIC1), a transcriptional repressor of CXCR7. Knockdown of p53 in MDA-MB-231 cells decreased HIC1 expression and further increased CXCR7 expression. However, overexpresion of p53 in MCF-7 increased HIC1 expression and further decreased CXCR7 expression. To investigate the function role of CXCR7 in breast cancer progression, Lentiviral expression and knockdown systems were used to overexpress CXCR7 in MDA-MB-231 cells and knockdown CXCR7 in MCF-7 cells, respectively. We observed that overexpression of CXCR7 in MDA-MB-231 cells promoted cell proliferation and migration whereas knockdown of CXCR7 in MCF-7 decreased the chemotaxis ability. Interestingly, the invasion ability was increased by knockdown of CXCR7 in MCF-7. Taken together, these results suggest that p53 mutant mediates CXCR7 expression and CXCR7 has multiple roles in breast cancer progression.