Abstract
17β-Estradiol (E2) stimulates morphological differentiation of an MCF-7 human mammary carcinoma cell line resulting in the development of multicellular rounded nodules (foci) above the epithelial monolayer. Examining the combined effect of progesterone (P4) and E2 on foci formation we detected P4-dependent foci enlargement and phenotypic modification. Notably, P4 dose-dependently potentiated lower dose E2-induced increases in foci numbers. We detected P4-dependent changes in cytoskeleton protein expression levels and accelerated cell division. P4 alone or in combination with E2 additively modified the expression of adhesion proteins and stimulated expression of tropomyosin (Tm). Antiprogestin and antiestrogen pretreatment abrogated P4-dependent increases in foci number and stimulation of Tm expression, indicating involvement of both E2 and P4 receptor signaling. Novel aspects of endocrine-regulated changes in microfilament and adhesion protein composition are discussed in association with tumorigenesis and metastatic capability in breast carcinoma cells.
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