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Cyr61, a Member of the CCN Family, Is Required for MCF-7 Cell Proliferation: Regulation by 17β-Estradiol and Overexpression in Human Breast Cancer.

Cyr61, a member of the CCN (CTGF/Cyr61/NOV) family of growth regulators, is a secreted cysteine-rich proangiogenic factor that has been implicated in tumorigenesis. Previous studies have also demonstrated that Cyr61 is regulated by 17β-estradiol (E2) in the uterus. Therefore, we hypothesized that hormonal regulation of Cyr61 may be important in estrogen-dependent pathogenic processes such as breast tumorigenesis. Our study demonstrates that both Cyr61 messenger RNA and protein are induced by E2 in MCF-7 mammary adenocarcinoma cells that primarily overexpress estrogen receptor α (ERα) in a dose-dependent and immediate early fashion. Cyr61 gene induction by E2 is transcriptionally regulated by ERα as the antiestrogen, ICI 182,780, and actinomycin D blocked induction completely. In addition, Cyr61 is up-regulated in MCF-7 cells by epidermal growth factor (EGF) in an immediate early fashion as well. The functional relevance of steroid induction of Cyr61 in breast cancer cell growth is demonstrated by anti-Cyr...