The increase in bladder carcinoma cell population induced by the free betasubunit of human chorionic gonadotrophin is a result of an anti-apoptosis effect and not cell proliferation

Ectopic production of free beta human chorionic gonadotrophin (hCG beta) by bladder carcinoma is well described and occurs in approximately 35% of cas es, hCG beta secreting tumours are more aggressive, radioresistant and have a greater propensity to metastasize. We proposed that the ectopic producti on of hCG beta was contributing in an autocrine fashion to the radioresista nce and metastatic potential of such secreting tumours. Though we demonstra ted that the addition of hCG beta to the culture media of bladder, cervical and endometrial carcinoma cell lines brought about an increase in cell pop ulations this was not accompanied by a significant increase in the rate of replication. Since a cell population size is a balance of mitosis and morta lity, we proposed that hCG beta was inhibiting apoptosis. Here we have demo nstrated that following incubation with recombinant hCG beta, bladder carci noma cells refrain from undergoing apoptosis. Quantitation of apoptotic bod ies was carried out by immunoassay and corrected to cell number as determin ed by MTT assay. In each cell line, addition of hCG beta reduced the number of apoptotic bodies dose-dependently, indicating a diminished apoptotic ra te. Furthermore, TGF beta 1-induced apoptosis could be dose-dependently inh ibited by co-incubation with hCG beta. We propose, therefore, that such a d ecline in apoptosis may account for the cell population increase previously reported. It may also explain the radioresistance and aggressive nature of hCG beta-secreting tumours and the poor prognosis associated therein. (C) 2000 Cancer Research Campaign.