Human activin type IIB receptor (ActRIIB) is a member of the TGF-β receptor superfamily. It mediates the actions of several ligands including activin A, myostatin, and GDF-11 to regulate cell growth, proliferation and differentiation. Dys-regulation of activin signal transduction such as reduced ActRIIB expression is associated with the development of high grade breast cancer in patients. This project aims to understand the mechanism by which ActRIIB regulates cell growth, proliferation and differentiation of breast cancer cells. First, we examined a number of human breast cancer cell lines and found that the level of expression of ActRIIB varies with different degree malignancy – its expression level is lower in the more malignant cancer cells. Since MCF-7, one of breast cancer cell line expresses a relatively higher level of ActRIIB, it is therefore chosen for our study to investigate the effects of knock-down of ActRIIB. Second, by using the siRNA approach, we observed that suppression of ActRIIB expression inhibits cell proliferation, and induces decreased telomerase activity and reduction in E-cadherin expression, suggesting that ActRIIB governs the proliferation, adhesion and migration of MCF-7 cells. To further substantiate our findings, we are using the shRNA approach to knock down ActRIIB cells. Specifically, we have generated the lentiviral vector directing expression of shRNA against ActRIIB. We will re-examine the effects of knockdown of ActRIIB in MCF-7 cells by shRNA. ActRIIB is a receptor protein with serine/threonine kinase activity. We hypothesize that the protein kinase activity of ActRIIB is indispensable to its action. Thus, another approach we use in our investigation is to over-express a kinase-dead mutant of recombinant ActRIIB and examine if it acts as a dominant negative mutant antagonising the action of the endogenous ActRIIB in MCF-7 cells. Our study of the signalling mechanism of ActRIIB in breast cancer cells will shed light on the mechanism governing cancer cell proliferation and migration.