We have immunohistochemically examined a large number of normal, hyperplastic, metaplastic and neoplastic tissues for presence of human chorionic gonadotropin (Alpha and Beta HCG). The hormone was present in normal fetus and placenta and in more than 75% of adult lung neoplasms (except SCLC) but not in normal adult tissues. It was also synthesized in tumors generated in athymic nude mice by v-Harvy ras transformed bronchial epithelial cells. Addition of purified Alpha and Beta HCG subunits to normal human bronchial epithelial cells revealed that Alpha plus Beta, but neither, alone, is a growth factor for these bronchial cells. These results indicate that HCG is a consistent marker for human lung tumors and that it may play a causal role in lung tumorigenesis as a growth factor for human bronchial epithelial cells. To examine these findings at the level of gene expression, we constructed probes for Alpha- and Beta-HCG mRNA expression and have identified human lung tumor cell lines which synthesize only one or the other HCG subunit. Human lung tumor cell lines do not detectably differ from normal bronchial epithelial cells in the state of methylation of the HCG genes.
