P5-07-07: Follistatin Suppresses In Vitro Growth of Breast Cancer Cells and Its Reduced Expression in Breast Cancer Associated with Poor Differentiation and Prognosis.

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Abstract Background: Bone morphogenetic protein (BMP) belongs to TGF-β superfamily, being widely involved in prenatal and postnatal development and homeostasis of various tissues and organs. BMP signaling has been implicated in tumorigenesis and disease progression of certain malignancies. Recent studies demonstrated a profound role played Noggin, a BMP antagonist in bone metastasis from breast cancer. Current study examined expression of Follistatin, another BMP antagonist in a breast cancer cohort, and its relevance to pathological and clinical parameters. Methods: Expression of Follistatin was examined in breast cancer tissues (n=93) and normal background tissues (n=30) using quantitative real time PCR and immunhistochemistry (IHC). The breast tissue samples were collected immediately after surgery. The clinical follow-up was routinely performed after surgery. The median follow-up period was 120 months (June 2004). Full-length human Follistatin coding sequence was cloned into a plasmid vector. Following transfection and verification, effect of Follistatin overexpression on cell growth was examined using an in vitro growth assay. Results: IHC revealed cytoplamic staining of Follistatin in mammary epithelial cells in breast tissues. The staining appeared to be weaker in breast cancer, but there was no significant difference in its transcripts levels compared with that of normal background tissues. Follistatin transcripts were decreased in both moderately differentiated and poorly differentiated tumors, p=0.0165 and p=0.0169 in comparison with well differentiated tumors respectively. Transcript levels of Follistatin in primary tumors tended to be lower in the patients with poor prognosis (33.8±14.7) including those patients had local recurrence, metastases and died of breast cancer, p=0.09 when compared with that of patients remained disease free (117.0±46.0). Its expression appeared particularly lower in the patients died of the disease (21.8±12.0), p=0.05 v.s. disease free. Over-expression of Follistatin exerted inhibitory effect on in vitro growth of MDA-MB-231 cells. Conclusions: Decreased expression of Follistatin in primary tumors of breast cancer correlates with poorer differentiation and mortality. Follistatin suppresses in vitro growth of breast cancer cells. It suggests that Follistatin is a negative regulator for tumor growth and disease progression of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-07.