No abstract

Three clones of ectopic hormone-producing cells from a single human neoplasm (bronchogenic carcinoma) show different rates of synthesis and secretion of chorionic gonadotropin and its alpha and beta subunits. For each clone, the amount of one or the other subunit always exceeded that of the complete hormone molecule. These findings may be analogous to unbalanced immunoglobulin chain synthesis in certain forms of myeloma.The "ectopic" production of protein hormones and other polypeptides by malignant tumors of nonendocrine tissues is now well established (1-3). It has been proposed that this phenomenon is the result of derepression of the genome in the malignant cell, resulting in the transcription of DNA that is repressed in the normal cell. Such a mechanism predicts that the tumor cell product should have the same structure as that product produced by the normal cell of origin. This simple derepression hypothesis has been challenged by the occasional finding of "abnormal" tumor products, as measured by competitive radioassay techniques (4-6). However, because it is now recognized that certain polypeptide hormones may be synthesized in precursor forms (7) and, in addition, may be rapidly metabolized in vivo once they are secreted into the general circulation (8), immunological differences between "native glandular" hormone and the circulating peptide need not reflect differences in the primary structures of the polypeptide chains as they are synthesized in the cell.It has recently been shown that the glycoprotein trophic hormones, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and chorionic gonadotropin (hCG) are heteropolymers composed of two dissimilar subunits; an alpha subunit that is nearly identical among the four hormones and a beta subunit that confers biologic specificity (9). Thus, for these proteins, additional opportunities for production by a tumor of an "abnormal" product exist. For example, there could be unbalanced synthesis of the two subunits or faulty assembly of the subunits into the complete molecule. Indeed, the presence of hCG-g without accompanying complete hCG or free alpha subunit has been demonstrated in the plasma and in tumor extracts from a patient with pancreatic carcinoma (10, 11).In order to examine whether isolated or unbalanced subunit synthesis observed in vivo might reflect metabolism of intact hCG molecules and to study the mechanisms underlying control and expression of ectopic hormone production, we have been establishing such tumors in dispersed cell culture. We describe in this report our findings with three clonal strains of cells derived from a bronchogenic carcinoma previously shown to secrete biologically active hCG both in vivo and in vitro (12). The results of these experiments show that although the different clones each produce complete hCG molecules, they also synthesize and secrete larger amounts of at least one of the free subunits, and the ratios of subunits produced are greatly different among the clones. MATERIALS AN...

No abstract