The free monomeric beta subunit of human chorionic gonadotrophin (hCG beta) and the recently identified homodimeric beta-beta subunit (hCG beta beta) both have autocrine growth effects.
The ectopic production of free hCG beta is a common phenomenon in epithelial tumours, a phenomenon originally believed to have no biological significance. However, it is now apparent that hCG beta may significantly effect tumour development by increasing cell populations through inhibition of apoptosis. The recently identified hCG beta beta homodimer, with topological similarities to cystine knot growth factors, has been suggested to be the responsible mediator of these novel tumourigenic responses. In this study we isolated hCG beta monomer from hCG beta beta homodimer using size exclusion chromatography and confirmed the separation by Western blotting. Using a tetrazolium bromide incorporation cell number quantification assay (MTT), we measured the growth effects of separated hCG beta fractions corresponding to monomeric (hCG beta) and dimeric (hCG beta beta) forms on the hCG beta responding cell line T24. Maximal increases in cell number corresponded to the elution peak of dimeric and monomeric hCG beta. In conclusion, it would appear that the recently observed hCG beta beta homodimer is no more bioactive than its monomeric counterpart, in stimulating bladder cancer cell growth. This strengthens the proposition that hCG beta may exert its antiapoptotic effects by antagonistic inhibition of other cystine knot growth factor receptors and not by a specific receptor-mediated homodimeric interaction as seen for its topological counterparts TGF, PDGF-B and NGF.
Butler
Stephen A
SA
Williamson Laboratory, Department of Obstetrics and Gynecology, Bart's and the London Queen Mary School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Iles
Ray K
RK
D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay; D015153:Blotting, Western; D002277:Carcinoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000494:pharmacology*; D002850:Chromatography, Gel; D004848:Epithelium / Q000473:pathology; D006801:Humans; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D018997:Chorionic Gonadotropin, beta Subunit, Human