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Biol Reprod. 2014 Oct;91(4):100. doi: 10.1095/biolreprod.114.120899. Epub 2014 Aug 27.

Soy promotes juvenile granulosa cell tumor development in mice and in the human granulosa cell tumor-derived COV434 cell line.

Author information

1
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.
2
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas spangas@bcm.edu.

Abstract

Soy attracts attention for its health benefits, such as lowering cholesterol or preventing breast and colon cancer. Soybeans contain isoflavones, which act as phytoestrogens. Even though isoflavones have beneficial health effects, a role for isoflavones in the initiation and progression of diseases including cancer is becoming increasingly recognized. While data from rodent studies suggest that neonatal exposure to genistein (the predominant isoflavone in soy) disrupts normal reproductive function, its role in ovarian cancers, particularly granulosa cell tumors (GCT), is largely unknown. Our study aimed to define the contribution of a soy diet in GCT development using a genetically modified mouse model for juvenile GCTs (JGCT; Smad1 Smad5 conditional double knockout mice) as well as a human JGCT cell line (COV434). While dietary soy cannot initiate JGCT development in mice, we show that it has dramatic effects on GCT growth and tumor progression compared to a soy-free diet. Loss of Smad1 and Smad5 alters estrogen receptor alpha (Esr1) expression in granulosa cells, perhaps sensitizing the cells to the effects of genistein. In addition, we found that genistein modulates estrogen receptor expression in the human JGCT cell line and positively promotes cell growth in part by suppressing caspase-dependent apoptosis. Combined, our work suggests that dietary soy consumption has deleterious effects on GCT development.

KEYWORDS:

apoptosis; endocrine disruptors; estrogen receptor; genistein; granulosa cells; ovarian cancer; ovary; soy

PMID:
25165122
PMCID:
PMC4435027
DOI:
10.1095/biolreprod.114.120899
[Indexed for MEDLINE]
Free PMC Article

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