The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines

Gillott, David J.; Iles, Ray K.; Chard, Tim

doi:10.1038/bjc.1996.56

Cited by 99 publications

(75 citation statements)

References 20 publications

(11 reference statements)

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“…It is now apparent that this event may significantly affect tumour development given the growth effects recently described (LunardiIskander et al, 1995;Gillott et al, 1996). It is accepted that free hCGβ is unable to activate the LH/hCG receptor and stimulate the subsequent second messengers.…”

Section: Discussionmentioning

confidence: 99%

“…T24 has been shown to be the most sensitive to the addition of hCGβ believed to be due to the fact that it produces no endogenous hCGβ of its own (Gillott et al, 1996). SCaBER and RT112 are high level hCGβ producers and 5637 and J82 low level hCGβ producers (Iles and Chard, 1989).…”

Section: Cell Linesmentioning

confidence: 99%

“…More recently, however, it has been shown that the beta subunit may have its own unique functions. LunardiIskander et al (1995) and Gillott et al (1996) have independently shown growth inhibitory and growth stimulatory effects of free hCGβ. Elucidation of the crystal structure of hCG revealed surprising topological similarities with the known 'cystine knot' growth factors -transforming growth factor beta (TGF-β), platelet derived growth factor beta (PDGFβ) and nerve cell growth factor (NGF).…”

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confidence: 98%

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et al. 2000

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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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Section: Discussionmentioning

confidence: 99%

Section: Cell Linesmentioning

confidence: 99%

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confidence: 98%

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“…hCG␤ has been shown to exert a growth-promoting effect in culture, 27 and in bladder cancer cells, this has been shown to result from inhibition of apoptosis. 28 No receptor for hCG␤ has been identified, but based on the structural similarity between hCG␤ and the so-called cysteine-knot growth factors, 29 eg, transforming growth factor ␤, platelet-derived growth factor-B, and nerve growth factor, it has been suggested that hCG␤ interferes with the growth-inhibiting effect of these through a paracrine or autocrine route.…”

Section: Hcg␤ In Renal Cellmentioning

confidence: 99%

Expression Of Human Chorionic Gonadotropin β-Subunit Type I Genes Predicts Adverse Outcome In Renal Cell Carcinoma

Hotakainen

Lintula

Ljungberg

et al. 2006

The Journal of Molecular Diagnostics

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Expression of the free ␤-subunit of human chorionic gonadotropin (hCG␤) in malignant tumors is frequently associated with aggressive disease. The pretreatment serum concentration of hCG␤ is an independent prognostic variable in renal cell carcinoma (RCC). The three so-called type II genes (hCG␤ 3/9, 5, and 8) have been shown to be up-regulated in relation to type I genes (hCG␤ 6/7) in some malignant tumors. We developed a reverse transcription-polymerase chain reaction method for quantification of relative levels of the mRNAs for the two types of hCG␤ genes and studied the association between the expression in RCC tissue (n ‫؍‬ 104) and clinical outcome. hCG␤ mRNA expression was detected in 40% (42 of 104) of the tumors, and in 40 of these (93%), this consisted of hCG␤ type I mRNA only, whereas type II hCG␤ mRNA was detected in two samples. hCG␤ mRNA expression was significantly associated with a shorter diseasespecific (log-rank P ‫؍‬ 0.023; median survival 1.4 versus 7.9 years) and overall survival (log-rank P ‫؍‬ 0.011). In a Cox regression model, stage (P < 0.0001) and hCG␤ mRNA expression (P < 0.0001) were independent prognostic variables. We conclude that expression of type I hCG␤ genes indicates adverse prognosis in

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“…However, it has now been shown that the -subunit may have its own unique functions. Lunardi-Iskandar et al (1995) and Gillott et al (1996) have shown growth inhibitory and growth stimulatory effects respectively of free hCG . Recently, elucidation of the crystal structure of hCG revealed a similar topology between hCG and transforming growth factor (TGF ), platelet derived growth factor (PDGF ) and nerve cell growth factor (NGF) (Lapthorn et al 1994, Wu et al 1994.…”

Section: Introductionmentioning

confidence: 99%

The beta-subunit of human chorionic gonadotrophin exists as a homodimer

Butler

Laidler²,

Porter³

et al. 1999

Journal of Molecular Endocrinology

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The free -subunit of human chorionic gonadotrophin (hCG ) 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 hCG 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 hCG .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 hCG contain hCG 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 hCG species, of approximately 32 and 64 kDa, were clearly resolved by SDS-PAGE and Western blotting. When analysed by MALDI-TOF MS a 23 kDa monomer and a 46 kDa dimer were identified.Formation of hCG 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 hCG preparations in tumours.

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The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines

Cited by 99 publications

References 20 publications

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Expression Of Human Chorionic Gonadotropin β-Subunit Type I Genes Predicts Adverse Outcome In Renal Cell Carcinoma

The beta-subunit of human chorionic gonadotrophin exists as a homodimer

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