SIRPalpha1 and SIRPalpha2: their role as tumor suppressors in breast carcinoma cells.
We have previously reported that expression of SIRPalpha1/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 SIRPalpha1 expression in breast cancer cell lines, Hs578T and MCF7, and compared with the effect of SIRPalpha2 expression in Hs578T. Forced expression of either SIRPalpha1 or SIRPalpha2 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 SIRPalpha1 or SIRPalpha2 displayed distinct suppressive effect on the anchorage-independent growth of Hs578T cells. Similarly, forced expression of SIRPalpha1 in MCF7 specifically suppressed the anchorage-independent growth of the cells. Taken together, our results strongly suggest the function of SIRPalpha1 and 2 as type II tumor suppressors for human breast carcinoma.
Yamasaki
Yukiko
Y
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Ito
Satoko
S
Tsunoda
Nobuyuki
N
Kokuryo
Toshio
T
Hara
Kazuo
K
Senga
Takeshi
T
Kannagi
Reiji
R
Yamamoto
Tatsuyoshi
T
Oda
Koji
K
Nagino
Masato
M
Nimura
Yuji
Y
Hamaguchi
Michinari
M
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000737:chemistry / Q000502:physiology*; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D022502:Stress Fibers / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000502:physiology*
D000943:Antigens, Differentiation; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D025521:Tumor Suppressor Proteins