Pretranslational regulation of ectopic hCG alpha production in ChaGo lung cancer cells by sodium butyrate.

Ectopic production of hCG and its free alpha subunit by ChaGo lung cancer cells is stimulated by sodium butyrate. To investigate pretranslational regulation in this system, we examined the response of the hCG alpha and beta subunit mRNAs in ChaGo-K1 cells, a clone that produces free hCG alpha but no hCG or hCG beta in the basal state. When a Northern blot of total RNA from ChaGo cells was hybridized to a [32P]- labeled hCG alpha cDNA probe, a single band was detected that was identical in size (approximately 850 bases) to placental hCG alpha mRNA. RNA from butyrate-stimulated (5 mM, 24 h) ChaGo cells contained 7.7 times as much hCG alpha mRNA as RNA from control ChaGo cells. This increase appeared to be relatively selective since no difference in total polyA-containing mRNA levels was detected between butyrate-treated and control cells by [32P]oligo(dT) hybridization. In addition, no hCG beta mRNA was detected when Northern and dot blots were hybridized to an hCG beta cDNA probe. In a time course experiment, hCG alpha mRNA accumulation in butyrate-treated cells increased significantly by 8 h with a maximum increase of 6.1-fold at 24 h compared to control values. Major differences in immunoactive hCG alpha accumulation were not apparent, however, until after 24 h. These studies show that stimulation of ChaGo hCG alpha production by butyrate can be completely accounted for by pretranslational events and that failure to detect hCG or free hCG beta production by these cells is not due to poorly translatable RNA or post-translational protein degradation. Thus, exclusive ectopic production of only one of the hCG subunits is likely to be due to selective genomic expression.