All-trans-retinoic acid alters myc gene expression and inhibits in vitro progression in small cell lung cancer.
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.
Kalemkerian
G P
GP
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Jasti
R K
RK
Celano
P
P
Nelkin
B D
BD
Mabry
M
M
D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D014212:Tretinoin