Influence of Human Luteinizing Hormone on Cell Growth and CA125 Secretion of Primary Epithelial Ovarian Carcinomas in vitro

Kurbacher, Christian M.; Jäger, Wolfram; Kurbacher, J.A.; Bittl, Andreas; Wildt, L.; Lang, N.

doi:10.1159/000217954

Cited by 21 publications

(11 citation statements)

References 19 publications

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“…Unlike the uncertainty as to the origin of high gonadotropin concentrations in the fluid from epithelial tumors of the ovary, sample evidence has been provided that gonadotropins support cell proliferation (Wimalsena et al 1992, Kurbacher et al 1995, Schiffenbauer et al 1997, Syed et al 2001 through receptors expressed by tumor cells (Mandai et al 1997, Parrot et al 2001.…”

Section: Resultsmentioning

confidence: 99%

FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

Rzepka-G√≥rska

Chudecka-G≈Çaz²,

Kosmowska³

2004

Endocr Relat Cancer

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The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n ¼ 14), benign cystadenomas (n ¼ 28) and simple cysts (n ¼ 44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group. The concentration of FSH and LH was measured in serum and tumor fluid and the serum/tumor fluid ratio was calculated. The results in each group were compared and the sensitivity, specificity, positive and negative predictive values were determined.Mean concentrations of both gonadotropins in ovarian cancer fluid were significantly higher than in the remaining groups (P ranged from <0.005 to <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH ¼ 2.91, LH ¼ 4.19).Our findings support the hypothesis that gonadotropins are involved in ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios could be of value in the differential diagnosis of functional and organic cysts of the ovary.

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Section: Resultsmentioning

confidence: 99%

FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

Rzepka-G√≥rska

Chudecka-G≈Çaz²,

Kosmowska³

2004

Endocr Relat Cancer

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“…One of the predominant theories is a gonadotropin theory that circulating levels of pituitary gonadotropins increase the risk of malignancy and that pregnancies and oral contraceptives protect by suppressing secretion of these hormones (Gardner 1961, Stadel 1975. Based on recent studies, treatments with FSH and LH/hCG seem to result in growth stimulation in normal, immortalized OSE and some ovarian cancer cells in a dose-and time-dependent manner in vitro (Wimalasena et al 1992, Kurbacher et al 1995, Kraemer et al 2001, Ohtani et al 2001, Parrott et al 2001, Syed et al 2001, Choi et al 2002, although there are controversial reports (Wimalasena et al 1991, Venn et al 1995, Ivarsson et al 2001, Tourgeman et al 2002. Despite these observations, whether gonadotropins may play a role in normal OSE biology and ovarian tumorigenesis remains to be fully elucidated and the exact mechanism of the response to gonadotropins is not clearly understood.…”

Section: Discussionmentioning

confidence: 99%

Gonadotropins upregulate the epidermal growth factor receptor through activation of mitogen-activated protein kinases and phosphatidyl-inositol-3-kinase in human ovarian surface epithelial cells

Choi¹

2005

Endocrine Related Cancer

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Gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have been implicated as probable risk factors in epithelial ovarian carcinomas, most of which are derived from ovarian surface epithelium (OSE). Since epidermal growth factor (EGF) increases the growth of ovarian surface epithelial cells, we determined the effect of gonadotropins on the expression of epidermal growth factor receptor (EGFR). We investigated the basal levels of EGFR mRNA and protein, and the mechanisms involved in the regulation of EGFR at the transcriptional and translational levels by FSH and LH. The immortalized OSE cell lines (IOSE) derived from normal OSE cells by transfecting SV40 T-antigen (IOSE-80 and IOSE-80PC, a post-crisis line) and ovarian cancer cell lines were employed. A significantly lower level of EGFR was observed in both IOSE-80 and IOSE-80PC cells when compared with the ovarian cancer cell lines, OVCAR-3 and SKOV-3. Treatment of IOSE-80PC cells with FSH and LH (10 -7 and 10 -6 g/ml) resulted in a significant increase in EGFR mRNA at 24 h and EGFR protein at 48 h, whereas the treatment with gonadotropins for 24-48 h induced a mild increase in EGFR in OVCAR-3, but not in SKOV-3 cells. In addition, IOSE-80PC cells treated with gonadotropins and EGF (10 nM) exhibited an additive stimulation of mitogenesis. Further, FSH and LH significantly increased activities of various kinases at 5-10 min, and pre-treatments with LY294002 (an inhibitor of PI3K) or PD98059 (an inhibitor of ERK1/2) partially blocked the gonadotropin-induced up-regulation of EGFR in IOSE-80PC cells. We investigated whether the effect of gonadotropins on EGFR mRNA levels is induced by increased transcription and/or by altered mRNA stability. Treatment of IOSE-80PC cells with FSH (10 -7 and 10 -6 g/ml) significantly enhanced the activity of the EGFR promoter (120 and 140% increase, respectively) at 24 h, and treatment with LH (10 -7 g/ml) for 24 h induced an increase in the activity of EGFR promoter (30%) in these cells. On the other hand, LH resulted in a significant increase in EGFR mRNA stability in the decay curves. Taken together, these results suggest that the effect of gonadotropins on the expression of EGFR may affect cell growth via ERK-1/-2 and PI3K pathways in preneoplastic ovarian surface epithelial cells, and that FSH and LH increase EGFR mRNA by different mechanisms. The former increased EGFR gene transcription essentially, whereas the latter mainly enhanced EGFR mRNA stability.

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“…Several experimental studies have shown that hCG can stimulate ovarian cancer growth [3][4][5][6]. Respective receptors have been detected immunohistochemically as well as on mRNA basis [7,[29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

“…In their experiments, tumors could only be induced when LH increased which led them to speculate that LH Steinmeyer/Berkholz/Gebauer/Jäger plays the crucial part for tumor development. Experiments with tissue cultures have shown that the growth of human ovarian cancer cell lines is stimulated by hCG and LH [3][4][5][6]. This was the case especially with cell lines derived from highly differentiated ovarian carcinomas.…”

Section: Introductionmentioning

confidence: 99%

The Expression of hCG Receptor mRNA in Four Human Ovarian Cancer Cell Lines Varies Considerably under Different Experimental Conditions

et al. 2003

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In the present study, expression and regulation of hCG receptor mRNA were analyzed in four established human ovarian cancer cell lines using different concentrations of hCG, EGF, and 8-bromo-cAMP for different periods between 6 and 72 h. The cells were examined for the hCG receptor using the reverse-transcriptase polymerase chain reaction with specific primers amplifying the hCG receptor gene. Receptor mRNA was found in all cell lines. In the line OVCAR-3, it was expressed in all samples independent of kind and concentration of the receptor agonist and incubation period. In the line COLO-704, the hCG receptor gene was expressed only in unstimulated samples, but not in the samples incubated with a receptor agonist. The cell line EFO-21 showed a downregulation of receptor mRNA after 24 h of treatment with 25 IU/ml hCG and after 6 h of treatment with 250 IU/ml hCG or 100 ng/ml EGF. The mRNA reappeared within 24–48 h. The cell line EFO-27 showed a downregulation of receptor mRNA after 6 h of incubation with 250 IU/ml hCG. Agarose gel electrophoresis and sequencing of the polymerase chain reaction products revealed four cDNA fragments resulting from an alternative splicing of the primary transcript. The results of the study demonstrate that the expression of hCG receptor mRNA in ovarian cancer cell lines varies considerably under different experimental conditions. We showed that ovarian cancer cells can produce hCG receptors when needed or wanted. The inherent mechanisms which rule this phenomenon need further evaluation.

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Influence of Human Luteinizing Hormone on Cell Growth and CA125 Secretion of Primary Epithelial Ovarian Carcinomas in vitro

Cited by 21 publications

References 19 publications

FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

Gonadotropins upregulate the epidermal growth factor receptor through activation of mitogen-activated protein kinases and phosphatidyl-inositol-3-kinase in human ovarian surface epithelial cells

The Expression of hCG Receptor mRNA in Four Human Ovarian Cancer Cell Lines Varies Considerably under Different Experimental Conditions

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