Mogi Y, Kato J, Horimoto M, Takimoto R, Murakami T, Hirayama A, Kohgo Y, Watanabe N, Niitsu Y
Department of Internal Medicine, Sapporo Medical University School of Medicine.
Jpn J Cancer Res. 1994 May;85(5):459-63. doi: 10.1111/j.1349-7006.1994.tb02380.x.
The mechanism of growth inhibition by transforming growth factor (TGF)-beta 1 was investigated. We examined the growth inhibitory effects of TGF-beta 1 on human nasopharyngeal carcinoma (KB) cells which constitutively expressed p53. TGF-beta 1 suppressed the DNA synthesis of KB cells in a dose-dependent manner. It had minimal effect on adenovirus-2-transduced KB cells expressing either adenovirus early region 1B (E1B) or 1A (E1A) product, which respectively binds to p53 or Rb product and inhibits its function, and no growth inhibition at all was observed with KB cells expressing both E1B and E1A products. Dephosphorylation of the p53 was promoted by TGF-beta 1 stimulation in KB cells, but not in E1B-producing KB cells, which sequestrate the function of p53. The growth inhibition of KB cells by TGF-beta 1 was significantly reduced by treatment with okadaic acid. These results suggest that p53 transduces the antiproliferative signal of TGF-beta 1 possibly through its dephosphorylation.
研究了转化生长因子（TGF）-β1抑制生长的机制。我们检测了TGF-β1对组成性表达p53的人鼻咽癌（KB）细胞的生长抑制作用。TGF-β1以剂量依赖的方式抑制KB细胞的DNA合成。它对表达腺病毒早期区域1B（E1B）或1A（E1A）产物的腺病毒2转导的KB细胞影响极小，E1B或E1A产物分别与p53或Rb产物结合并抑制其功能，而对于同时表达E1B和E1A产物的KB细胞则完全未观察到生长抑制作用。在KB细胞中，TGF-β1刺激可促进p53的去磷酸化，但在使p53功能失活的产生E1B的KB细胞中则不然。用冈田酸处理后，TGF-β1对KB细胞的生长抑制作用显著降低。这些结果表明，p53可能通过其去磷酸化转导TGF-β1的抗增殖信号。
