The Free Monomeric Beta Subunit of Human Chorionic Gonadotrophin (hCGβ) and the Recently Identified Homodimeric Beta-Beta Subunit (hCGββ) both Have Autocrine Growth Effects

Abstract

The ectopic production of free hCGβ is a common phenomenon in epithelial tumours, a phenomenon originally believed to have no biological significance. However, it is now apparent that hCGβ may significantly effect tumour development by increasing cell populations through inhibition of apoptosis. The recently identified hCGββ 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 hCGβ monomer from hCGββ 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 hCGβ fractions corresponding to monomeric (hCGβ) and dimeric (hCGββ) forms on the hCGβ responding cell line T24. Maximal increases in cell number corresponded to the elution peak of dimeric and monomeric hCGβ. In conclusion, it would appear that the recently observed hCGββ homodimer is no more bioactive than its monomeric counterpart, in stimulating bladder cancer cell growth. This strengthens the proposition that hCGβ 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.