Introduction of the c-kit gene leads to growth suppression of a breast cancer cell line, MCF-7.
Normal ductal cells of the breast are exceptional on that their epithelial cells abundantly express the c-kit receptor. Loss of c-kit expression has been reported in 80-90% of breast cancer specimens, suggesting a possible role in the development of tumors. In the present study, we introduced a c-kit expression vector into a breast cancer cell line. MCF-7, which does not express c-kit but does express its ligand, stem cell factor (SCF). Anchorage dependent and independent growth was found to be inhibited in bulk cultures of the c-kit transfectants, although this suppression appeared to be incomplete, allowing a considerable fraction to tolerate c-kit expression. Heterogeneous sensitivity to the suppressive effects mediated by the c-kit receptor was also observed among individual clones isolated from the bulk cultures. These results suggest that c-kit can mediate inhibitory signals for the growth of breast cancer cells, but that cellular heterogeneity exists regarding the response. Further studies are warranted to elucidate the molecular basis for the inhibitory effects of c-kit.
Nishida
K
K
Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Nagoya, Japan.
Tsukamoto
T
T
Uchida
K
K
Takahashi
T
T
Takahashi
T
T
Ueda
R
R
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D009363:Neoplasm Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit