Suppression of tumorigenicity in breast cancer cells by the microfilament protein profilin 1

Differential display screening was used to reveal differential gene express ion between the tumorigenic breast cancer cell line CAL51 and nontumorigeni c microcell hybrids obtained after transfer of human chromosome 17 into CAL 51. The human profilin 1 (PFN1) gene was found overexpressed in the microce ll hybrid clones compared with the parental line, which displayed a low pro filin 1 level. A comparison between several different tumorigenic breast ca ncer cell lines with nontumorigenic lines showed consistently lower profili n 1 levels in the tumor cells. Transfection of PFN1 cDNA into CAL51 cells r aised the profilin 1 level, had a prominent effect on cell growth, cytoskel etal organization and spreading, and suppressed tumorigenicity of the stabl e, PFN1-overexpressing cell clones in nude mice. Immunohistochemical analys is revealed intermediate and low levels of profilin 1 in different human br east cancers. These results suggest profilin 1 as a suppressor of the tumor igenic phenotype of breast cancer cells.