Wang S J, Scavetta R, Lenz H J, Danenberg K, Danenberg P V, Schönthal A H
Department of Microbiology, University of Southern California, Los Angeles 90033-1054.
Carcinogenesis. 1995 Mar;16(3):637-41. doi: 10.1093/carcin/16.3.637.
The mechanism by which tumor promoters contribute to cellular transformation and tumorigenesis is not completely understood. To investigate further the molecular events involved in these processes, we used okadaic acid, a non-phorbol ester type tumor promoter that specifically inhibits certain protein phosphatases. We describe here that the continuous treatment of murine NIH 3T3 fibroblast cell cultures with okadaci acid resulted in a 50-fold amplification of two genes, mdr-1a and mdr-1b, that conferred multidrug resistance. As a consequence, the cells became cross-resistant to the cytotoxic effects of adriamycin, an antineoplastic drug used in the treatment of human tumors. Since genetic changes have been correlated with cell transformation and tumorigenesis, our results suggest that these processes may constitute an additional factor contributing to tumor promotion by okadaic acid.
肿瘤促进剂导致细胞转化和肿瘤发生的机制尚未完全明确。为了进一步研究这些过程中涉及的分子事件，我们使用了冈田酸，一种非佛波酯类肿瘤促进剂，它能特异性抑制某些蛋白磷酸酶。我们在此描述，用冈田酸持续处理小鼠NIH 3T3成纤维细胞培养物会导致两个赋予多药耐药性的基因mdr-1a和mdr-1b扩增50倍。结果，这些细胞对用于治疗人类肿瘤的抗肿瘤药物阿霉素的细胞毒性作用产生了交叉耐药性。由于基因变化与细胞转化和肿瘤发生相关，我们的结果表明，这些过程可能是冈田酸促进肿瘤发生的另一个因素。
