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.
Ectopic production of free beta human chorionic gonadotrophin (hCGbeta) by bladder carcinoma is well described and occurs in approximately 35% of cases. hCGbeta secreting tumours are more aggressive, radioresistant and have a greater propensity to metastasize. We proposed that the ectopic production of hCGbeta was contributing in an autocrine fashion to the radioresistance and metastatic potential of such secreting tumours. Though we demonstrated that the addition of hCGbeta 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 hCGbeta was inhibiting apoptosis. Here we have demonstrated that following incubation with recombinant hCGbeta, 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 hCGbeta reduced the number of apoptotic bodies dose-dependently, indicating a diminished apoptotic rate. Furthermore, TGFbeta1-induced apoptosis could be dose-dependently inhibited by co-incubation with hCGbeta. 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 hCGbeta-secreting tumours and the poor prognosis associated therein.
Butler
S A
SA
Department of Obstetrics and Gynecology, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
Ikram
M S
MS
Mathieu
S
S
Iles
R K
RK
D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000502:physiology*; D006801:Humans; D016212:Transforming Growth Factor beta / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D018997:Chorionic Gonadotropin, beta Subunit, Human; D016212:Transforming Growth Factor beta