Kalemkerian G P, Jasti R K, Celano P, Nelkin B D, Mabry M
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Cell Growth Differ. 1994 Jan;5(1):55-60.
Transitions between the small cell lung cancer and the non-small cell lung cancer phenotype occur during clinical tumor progression in small cell lung cancer. We have previously developed a culture model which mimics these transitions. In our model, the insertion of the v-Ha-ras oncogene into c-myc overexpressing NCI-H82 small cell lung cancer cells induces features characteristic of non-small cell lung cancer. We now report that treatment of NCI-H82 cells with 1 microM all-trans-retinoic acid resulted in decreased cellular growth, decreased c-myc mRNA levels, and increased L-myc mRNA levels. Retinoic acid treatment prior to v-Ha-ras insertion also inhibited the typical ras-induced phenotypic transition seen in untreated NCI-H82 cells. In contrast, retinoic acid treatment of NCI-H82 ras cells after ras-induced transition to the non-small cell lung cancer phenotype did not affect cellular phenotype, nor c-myc or L-myc gene expression. These data show that all-trans-retinoic acid, a clinically relevant compound, inhibits small cell lung cancer progression in our in vitro model and alters the expression of the c-myc and L-myc oncogenes. These findings suggest mechanisms for the biological effects of retinoic acid in small cell lung cancer.
在小细胞肺癌的临床肿瘤进展过程中，会发生小细胞肺癌和非小细胞肺癌表型之间的转变。我们之前开发了一种模拟这些转变的培养模型。在我们的模型中，将v-Ha-ras癌基因插入过表达c-myc的NCI-H82小细胞肺癌细胞中，可诱导出非小细胞肺癌的特征。我们现在报告，用1微摩尔全反式维甲酸处理NCI-H82细胞会导致细胞生长减少、c-myc mRNA水平降低以及L-myc mRNA水平升高。在插入v-Ha-ras之前用维甲酸处理也会抑制未处理的NCI-H82细胞中典型的ras诱导的表型转变。相比之下，在ras诱导向非小细胞肺癌表型转变后，用维甲酸处理NCI-H82 ras细胞不会影响细胞表型，也不会影响c-myc或L-myc基因表达。这些数据表明，全反式维甲酸这种临床相关化合物在我们的体外模型中可抑制小细胞肺癌进展，并改变c-myc和L-myc癌基因的表达。这些发现提示了维甲酸在小细胞肺癌中生物学效应的机制。
