Received for publication June 12, 2007.
Revised September 24, 2007.
Accepted for publication October 18, 2007.

Genistein induces phenotypic reversion of endoglin deficiency in human prostate cancer cells

Abstract

Genistein has been shown to inhibit human prostate cancer (PCa) cell motility. Endoglin has been identified as an important suppressor of PCa cell motility, and its expression is lost during PCa progression. It is therefore important to determine whether endoglin loss affects genistein's efficacy, and if so, by what mechanism. In the current study, genistein was shown to induce reversion of endoglin deficient cells to a low motility, endoglin replete, phenotype. As endoglin suppresses PCa cell motility in an ALK2 and Smad1 dependent manner, we sought to determine whether genistein was activating the ALK2-Smad1 pathway. While treatment with genistein, or over expression of Smad1 or ALK2, all increased Smad1 responsive promoter activity and decreased cell motility, genistein's efficacy was abrogated by either Smad1 or ALK2 knock down. Further, transfection of cells with a kinase dead mutant of ALK2 abrogated genistein's efficacy. Together, these findings demonstrate that genistein therapeutically induces reversion to a low motility phenotype in aggressive endoglin deplete PCa cells. It does so by activating ALK2-Smad1 endoglin-associated signaling. These findings support the notion that individuals with low endoglin expressing PCa will benefit from genistein treatment.

Key words: Metastasis, Tumor suppressors

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