Abstract
Ectopic production of free beta human chorionic gonadotrophin (hCGβ) by bladder carcinoma is well described and occurs in approximately 35% of cases. hCGβ secreting tumours are more aggressive, radioresistant and have a greater propensity to metastasize. We proposed that the ectopic production of hCGβ was contributing in an autocrine fashion to the radioresistance and metastatic potential of such secreting tumours. Though we demonstrated that the addition of hCGβ to the culture media of bladder, cervical and endometrial carcinoma cell lines brought about an increase in cell populations this was not accompanied by a significant increase in the rate of replication. Since a cell population size is a balance of mitosis and mortality, we proposed that hCGβ was inhibiting apoptosis. Here we have demonstrated that following incubation with recombinant hCGβ, bladder carcinoma cells refrain from undergoing apoptosis. Quantitation of apoptotic bodies was carried out by immunoassay and corrected to cell number as determined by MTT assay. In each cell line, addition of hCGβ reduced the number of apoptotic bodies dose-dependently, indicating a diminished apoptotic rate. Furthermore, TGFβ1-induced apoptosis could be dose-dependently inhibited by co-incubation with hCGβ. We propose, therefore, that such a decline in apoptosis may account for the cell population increase previously reported. It may also explain the radioresistance and aggressive nature of hCGβ-secreting tumours and the poor prognosis associated therein. © 2000 Cancer Research Campaign
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References
Braunstein GD (1983) hCG expression in trophoblastic and nontrophoblastic tumors. In: Oncodevelopmental Markers: Biologic, Diagnostic and Monitoring Aspects, Fishman WH (ed), pp. 35 Academic Press: New York
Butler SA, Laidler P, Porter JR, Kicman AT, Chard T, Cowan DA and Iles RK (1999) The beta subunit of human chorionic gonadotrophin exists as a homodimer. J Mol Endocrinol 22: 185–192
Cole LA, Wang Y, Elliot M, Latif M, Chambers JT, Chambers SK and Schwartz PE (1988) Urinary human chorionic gonadotrophin free β-subunit and core fragmant: a new marker of gynecological cancers. Cancer Res 48: 1356–1360
Gillott DJ, Iles RK and Chard T (1996) The effects of βhCG on the in vitro growth of bladder cancer cells. Br J Cancer 73: 323–326
Iles RK and Chard T (1989) Immunochemical analysis of the human chorionic gonadotrophin-like material secreted by ‘normal’ and neoplastic urothelial cells. J Mol Endocrinol 2: 107–112
Iles RK, Butler SA and Jacoby E (1999) Dimerisation of urinary β-core/hCGβcf: A cause of poor β-core assay performance in Downs syndrome screening studies. Prenatal Diagnosis 19: 790–792
Lapthorn AJ, Harris DC, Littlejohn A, Lustbader JW, Canfield RE, Machin KJ, Morgan FJ and Isaacs NW (1994) Crystal structure of hCG. Nature 369: 455–461
Lunardi-Iskandar Y, Bryant JL, Zeman RA, Lam VH, Samaniego F, Besnier JM, Hermans P, Thierry AR, Gill P and Gallo RC (1995) Tumorigenesis and metastasis of neoplastic Kaposi’s sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone. Nature 375: 64–68
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55–63
Pierce JG and Parsons TF (1981) Glycoprotein hormones: structure and function. Ann Rev Biochem 50: 465–495
Sporn MB, Roberts AB, Wakefield LM and Assoian RK (1986) Transforming growth factor-β: biological function and chemical structure. Science 233: 532–534
Sun PD and Davies DR (1995) The cystine-knot growth-factor superfamily. Ann Rev Biophys Biomol Struct 24: 269–291
Twentyman PR and Luscome M (1987) A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. Br J Cancer 56: 279–285
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Butler, S., Ikram, M., Mathieu, S. et al. The increase in bladder carcinoma cell population induced by the free beta subunit of human chorionic gonadotrophin is a result of an anti-apoptosis effect and not cell proliferation. Br J Cancer 82, 1553–1556 (2000). https://doi.org/10.1054/bjoc.2000.1177
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DOI: https://doi.org/10.1054/bjoc.2000.1177
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