We have previously reported that expression of SIRP alpha 1/SHPS-1 was strongly suppressed in v-Sre-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 SIRP alpha 1 expression in breast cancer cell lines, Hs578T and MCF7, and compared with the effect of SIRP alpha 2 expression in Hs578T. Forced expression of either SIRP alpha 1 or SIRP alpha 2 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 SIRP alpha 1 or SIRP alpha 2 displayed distinct suppressive effect on the anchorage-independent growth of Hs578T cells. Similarly, forced expression of SIRP alpha 1 in MCF7 specifically suppressed the anchorage-independent growth of the cells. Taken together, our results strongly suggest the function of SIRP alpha 1 and 2 as type II tumor suppressors for human breast carcinoma. (c) 2007 Elsevier Inc. All rights reserved.