Nishida K, Tsukamoto T, Uchida K, Takahashi T, Takahashi T, Ueda R
Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Nagoya, Japan.
Anticancer Res. 1996 Nov-Dec;16(6B):3397-402.
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.
乳腺的正常导管细胞很特别,因为其上皮细胞大量表达c-kit受体。据报道,在80%-90%的乳腺癌标本中c-kit表达缺失,提示其在肿瘤发生过程中可能发挥作用。在本研究中,我们将一个c-kit表达载体导入一种乳腺癌细胞系MCF-7,该细胞系不表达c-kit,但表达其配体干细胞因子(SCF)。在c-kit转染子的大量培养物中发现贴壁依赖性和非依赖性生长均受到抑制,尽管这种抑制似乎并不完全,仍有相当一部分细胞能够耐受c-kit表达。从大量培养物中分离出的单个克隆之间也观察到对c-kit受体介导的抑制作用存在异质性敏感性。这些结果表明,c-kit可以介导对乳腺癌细胞生长的抑制信号,但细胞对其反应存在异质性。有必要进一步研究以阐明c-kit抑制作用的分子基础。