Chorionic gonadotropin synthesis by human tumor cell lines: examination of subunit accumulation, steady-state levels of mRNA, and gene structure

Abstract

A number of tumor cell lines have been examined that differentially produce human chorionic gonadotropin and the isolated α- or β-subunits. It has been demonstrated that all of the cell lines studied to date contain genes for both α- and β-subunits, indicating that differential and exclusive expression of one subunit is not the result of a particular cell line having lost the gene for the alternate subunit as a consequence of chromosome changes accompanying cell transformation. Because many of these established cell lines are aneuploid, it is also significant that no evidence was found for gene amplification in cell lines producing α-subunit at very high levels compared to those with very low level expression. Analysis of restriction endonuclease digests of tumor cell DNAs has demonstrated identical patterns for β-subunit in KpnI digests and KpnI/ HinIII double digests. Polymorphisms were observed for α-subunit in EcoRI and HinIII digests, but these did not correspond with expression of the α-subunit. Significant levels of either mRNA (as determined by dot blot and Northern transfer hybridization analysis) were accompanied by corresponding elevated levels of α- and β-subunits (as determined by radioimmunoassay), suggesting that regulation of subunit production most likely occurs at a pretranslational stage. However, there were apparent differences in the relative ratio of α- and β-subunits and their cognate mRNAs among the cell lines.