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R. K. Iles and T. Chard


Material with the immunochemical characteristics of human chorionic gonadotrophin (hCG) is produced by bladder tumour cells in vitro and in vivo. In order to characterize this material further, media were collected from 17 cell cultures (three choriocarcinomas, seven bladder carcinomas and seven 'normal' urothelium). The hCG-like material was compared with pregnancy hCG and purified α- and β-subunits by specific radioimmunoassays. Media were also submitted to affinity chromatography and the fractions further analysed by SDS-PAGE and Western blotting. It was shown that both the neoplastic and normal urothelium produced only free β-subunit-like material. This urothelial 'β-hCG' has the same molecular weight and electrophoretic mobility as that present in the intact hCG of pregnancy.

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R K Iles and T Chard

Although discovered in the early 1930s, much of the biochemistry and molecular biology of human chorionic gonadotrophin (hCG) has only recently been revealed. The sequence was described in 1973 (Bellisario et al. 1973; Carlsen et al. 1973), but the precise secondary and tertiary structures are still unknown. Only in the last 5 years has there been dramatic progress in the understanding of the molecular nature of this hormone. These studies shed light on many clinical aspects of the biology of hCG, including its association with non-trophoblastic epithelial cancers.

CG and the glycoprotein hormones

Chorionic gonadotrophin is a member of a group of four structurally homologous proteins commonly referred to as the glycoprotein hormones. As the name implies, the hormone protein chains are glycosylated; hCG contains approximately 30% carbohydrate by weight. The other members are luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH). CG differs from the other glycoprotein

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R. K. Iles, B. H. Czepulkowski, B. D. Young, and T. Chard


The β-subunit of human chorionic gonadotrophin (hCG) is coded on chromosome 19 by the β-hCG-hLH gene cluster. Genomic DNA has been isolated from bladder tumour cell lines which ectopically express β-hCG. The β-hCG—hLH gene cluster was probed for possible rearrangement or amplification and cells karyotyped for chromosome 19 abnormalities. No rearrangement or amplification of the gene cluster and no consistent abnormalities of chromosome 19 were found. The expression of β-hCG by bladder tumours is therefore likely to be the result of altered gene regulation and not a rearrangement or amplification of this gene cluster.

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SA Butler, P Laidler, Porter JR, AT Kicman, T Chard, DA Cowan, and RK Iles

The free beta-subunit of human chorionic gonadotrophin (hCGbeta) is well recognised as a product of many epithelial tumours. Recently, it has been shown that this ectopic production may have a functional relationship to tumour growth. The growth-promoting activity of hCGbeta may be explained by its structural similarity to a family of growth factors which all contain the same distinct topological fold known as the cystine-knot motif. Since the other members of this family all exhibit their activities as homo- and heterodimers, it is possible that the same may be true for hCGbeta. Using size-exclusion chromatography, low stringency SDS-PAGE and matrix assisted laser desorption/ionisation (MALDI) time-of-flight (TOF) mass spectrometry (MS) we have shown that pure preparations of hCGbeta contain hCGbetabeta homodimers. Size-exclusion chromatography revealed asymmetric elution profiles with a forward peak corresponding to the size-exclusion characteristic of a globular protein with an approximate mass of 44-54 kDa and a late shoulder centered around an elution position expected for a globular protein of approximately 29 kDa. Two immunoreactive hCGbeta species, of approximately 32 and 64 kDa, were clearly resolved by SDS-PAGE and Western blotting. When analysed by MALDI-TOF MS a |mf23 kDa monomer and a |mf46 kDa dimer were identified. Formation of hCGbetabeta homodimers is consistent with the behaviour of other cystine-knot growth factors and strengthens the inclusion of the glycoprotein hormones within this superfamily. It has yet to be determined whether it is this dimeric molecular species that is responsible for growth-promoting activity of hCGbeta preparations in tumours.