Messenger ribonucleic acid expression of LH/hCG receptor gene in human ovarian carcinomas

Mandai, Masaki; Konishi, Ikuo; Kuroda, Hisao; Fukumoto, Manabu; Komatsu, Toshiaki; Yamamoto, Shinya; Nanbu, Kanako; Rao, Ch.V.; Mori, Takahide

doi:10.1016/s0959-8049(97)00166-4

Cited by 63 publications

(48 citation statements)

References 52 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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“…Reduced risk of ovarian cancer is associated with multiple pregnancies, breast feeding, oral contraceptives and estrogen replacement therapy, which are associated with lower levels of and reduced exposure to gonadotropins (Daly & Obrams 1998, Gnagy et al 2000, La Vecchia 2001. The expressions of FSHR and LHR in normal and neoplastic OSE cells have been demonstrated (Kobayashi et al 1996, Mandai et al 1997, Minegishi et al 2000, Zheng et al 2000, Parrott et al 2001. Recent studies suggest the relationship between expression of gonadotropin receptor and ovarian cancer development (Lu et al 2000, Syed et al 2001, Wang et al 2003.…”

Section: Introductionmentioning

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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“…86,87 This splice variant appeared to be up-regulated in endometrial adenocarcinoma but lost in ovarian cancer as compared with the respective nonneoplastic tissues of tumor origin. 88,89 Moreover, potential additional LH/hCG receptor spliceoforms were observed in endometrial cancer. 88 The biological significance and clinical potential of LH/hCG splice variants in gynecological malignancies is undetermined.…”

Section: Other G Protein-coupled Receptorsmentioning

confidence: 99%