Study On The Relationship Between Activin A And Breast Cancer

Activin is a member of the transforming growth factor-β(TGF-β) superfamily of growth factors and was initially isolated in 1986 based on its ability to stimulate follicle-stimulating hormone secretion from the anterior pituitary. Activin has several biological functions, including regulation of cell proliferation, differentiation and apoptosis.Activin signaling has been associated with mammary cell growth inhibition as well as regulation of mammary glandular development. Activin and its receptors are expressed during postnatal mouse mammary development and glandular formation during the lactating phase. Activin receptors and signaling molecules are present in human breast cancer cell lines, these results suggest that the expression of activin A has close relationship with breast tumorigenisis and progression. However there is a little research about this area.To investigate the relationship between the expression of activin A and human breast cancer, we first isolated the N-terminal region sequence of activin beta A subunit and expressed the the recombinent protein of of activin beta A subunit through pET-28a (+) / BL21 prokaryotic expression system, then the activin beta A recombinant protein with poly-His tag in the N-terminal was purified by Ni2+ affinity chromatography. Polyclonal antibody against activin beta A was generated by immunizing rabbit with purfied His-tagged activin beta A protein. We next determined the frequency and distribution of activin beta A subunit in the tissues including breast hyperplastic, fibroadenoma, mucous adenocarcinoma, tracheal carcinoma and carcinoma simplex, and further investigate the association of the frequency and distribution of activin beta A subunit with malignant progression, tumor size, tumor grade and metastases by Immunohistochemistry method. The result showed significant correlations in breast cancer specimens between a decrease of activin beta A abundance and high tumor malignant progression, high tumor grade, and high tumor metastases.To further investigate the functions of activin A in breast tumorigenisis, we constructed pcDNA3-ActA recombinenet vector and transfected into human breast cancer cell line MDA-MB-231 cells, and investigate the effect of activin A on the proliferation of MDA-MB-231 cells. The result shown that overexpression of activin A significantly reduced the proliferation of MDA-MB-231 cells and the survival in serum-free medium.These results suggesting that activin A as a tumor suppressor, it low expression has close relationship with breast tumorigenisis, high tumor malignant progression, high tumor grade, and high tumor metastases.This study established a necessary basic for elucidating of the mechanism of breast tumorigenesis and has a significant value for the diagnosis and treatment of breast cancer.