SIRPα1 and SIRPα2: Their role as tumor suppressors in breast carcinoma cells

We have previously reported that expression of SIRPα1/SHPS-1 was strongly suppressed in v-Src-transformed cells and its forced expression resulted in the suppression of anchorage-independent growth of the cells [K. Machida, S. Matsuda, K. Yamaki, T. Senga, A.A. Thant, H. Kurata, K. Miyazaki, K. Hayashi, T. Okuda, T. Kitamura, T. Hayakawa, M. Hamaguchi, v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells, Oncogene 19 (2000) 1710–1718]. We examined the effect of human SIRPα1 expression in breast cancer cell lines, Hs578T and MCF7, and compared with the effect of SIRPα2 expression in Hs578T. Forced expression of either SIRPα1 or SIRPα2 did not perturb the growth of Hs578T in a conventional attached condition. Their expression, however, enforced the actin stress fiber formation and induced activation of Rho, but not Rac, in Hs578T cells. Moreover, forced expression of either SIRPα1 or SIRPα2 displayed distinct suppressive effect on the anchorage-independent growth of Hs578T cells. Similarly, forced expression of SIRPα1 in MCF7 specifically suppressed the anchorage-independent growth of the cells. Taken together, our results strongly suggest the function of SIRPα1 and 2 as type II tumor suppressors for human breast carcinoma.