Luo W, Wood C G, Earley K, Hung M C, Lin S H
Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Oncogene. 1997 Apr 10;14(14):1697-704. doi: 10.1038/sj.onc.1200999.
C-CAM1 is an epithelial adhesion molecule of immunoglobulin supergene family and has been implicated in the growth suppression of prostate cancer cells. Here we show that C-CAM1 can also suppress the tumorigenicity of breast cancer cells. These observations suggest that C-CAM1 may be a general growth suppressor in epithelial cells. In addition, we have identified the cytoplasmic domain, but not the extracellular adhesion domain, of C-CAM1 as critical for the growth suppression. Thus, the adhesion and the growth suppression functions of C-CAMI are independent of each other. Furthermore, mutation at the tyrosine phosphorylation site in the cytoplasmic domain of C-CAM1 did not obliterate C-CAM1's growth suppression function, suggesting that tyrosine phosphorylation is not involved in the signal transduction pathway leading to cell growth suppression. These studies provide the structural basis for future development of therapeutics that may selectively activate C-CAM1's growth suppression function.
C-CAM1是免疫球蛋白超基因家族的一种上皮粘附分子，与前列腺癌细胞的生长抑制有关。在此我们表明，C-CAM1也能抑制乳腺癌细胞的致瘤性。这些观察结果表明，C-CAM1可能是上皮细胞中的一种普遍生长抑制因子。此外，我们已确定C-CAM1的胞质结构域而非细胞外粘附结构域对生长抑制至关重要。因此，C-CAMI的粘附功能和生长抑制功能相互独立。此外，C-CAM1胞质结构域中酪氨酸磷酸化位点的突变并未消除C-CAM1的生长抑制功能，这表明酪氨酸磷酸化不参与导致细胞生长抑制的信号转导途径。这些研究为未来开发可能选择性激活C-CAM1生长抑制功能的治疗方法提供了结构基础。
