Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women

Noguchi, Toshifumi; Kitawaki, Jo; Tamura, Takeyuki; Kim, Tomoko; Kanno, Hiroshi; Yamamoto, Takara; Okada, Hiroji

doi:10.1016/0960-0760(93)90275-2

Cited by 35 publications

(15 citation statements)

References 7 publications

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“…A marked downregulation of progesterone receptor mRNA expression was noted in ovarian cancer cell lines when compared with normal ovarian surface epithelium cells [39]. Moreover, progesterone receptor immunopositivity was observed in the majority of borderline tumors, whereas a large percentage (93%) of malignant ovarian tumors stained negative for progesterone receptor [40]. Thus, loss of progesterone receptor maybe involved in the etiology and progression of ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of progesterone receptor expression in ovarian cancer: a meta-analysis

Luo

Zhao

et al. 2017

Oncotarget

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ObjectiveWhile a prognosis value of progesterone receptor (PR) in ovarian cancer has been reported in some publications, controversial data were presented by different reports. In order to address the disagreement of progesterone receptor in ovarian cancer survival, we conducted this meta-analysis.MethodsRelevant articles on progesterone receptor and ovarian cancer prognosis were identified via a thorough search of PubMed, Embase and Cochrane Central. Hazard ratios (HR) and 95% confidence interval (CI) were extracted from studies on overall survival (OS) and disease-free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS).ResultA total of 28 eligible studies containing 5685 patients were collected for analysis. It was found that progesterone receptor positivity was significantly associated with favorable overall survival (OS) (HR = 0.86, 95% CI = 0.78 to 0.95, P = 0.002) and disease-free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS) (HR = 0.75, 95% CI = 0.61 to 0.93, P = 0.008) of ovarian cancer patients. Subgroup analysis showed that progesterone receptor expression was associated with a favorable prognosis of unclassified ovarian cancer, European origin, and immunohistochemical detection method.ConclusionProgesterone receptor expression can be used as a favorable prognostic predictor in ovarian cancer managements.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of progesterone receptor expression in ovarian cancer: a meta-analysis

Luo

Zhao

et al. 2017

Oncotarget

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“…Lee et al [38] reported 86% of ovarian tumor specimens stained positive for ER, 50% positive for PR, and 45% positive for both receptors. In another study, PR immunopositivity was observed in the majority of borderline tumors, whereas almost all (93%) malignant ovarian tumors stained negative for PR [39]. Among the various OCa subtypes, ER-alpha immunostaining was found in 97% of serous adenocarcinomas, 100% of endometrioid adenocarcinomas, 70% of mucinous adenocarcinomas and none of the clear cell carcinoma specimens (0%) [40].…”

Section: Expression Of Progesterone and Estrogen Receptors In Ose Andmentioning

confidence: 99%

Untitled

2003

Reprod Biol Endocrinol

215

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Ovarian carcinoma (OCa) continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE) and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT) continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

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“…In a recent epidemiological study, an increase in ovarian cancer incidence was observed among women with progesterone deficiency (40). In another study, 93% of malignant ovarian tumors exhibited PR immunonegativity, whereas PR immunopositivity was observed in the majority of borderline tumors (41). Exposure of ovarian cancer cells to progesterone up-regulated p53 and induced apoptosis in ovarian cancer cell lines (42).…”

Section: Fig 2 Sequence Analyses Of the Wild-type Er␣ Transcript (Ementioning

confidence: 99%

Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells

Lau

Mok

1999

Proc. Natl. Acad. Sci. U.S.A.

253

161

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Our understanding of the roles played by sex hormones in ovarian carcinogenesis has been limited by a lack of data concerning the mode of sex hormone action in human ovarian surface epithelial (HOSE) cells, the tissue of origin of >90% of ovarian cancers. We have compared the relative abundance of estrogen receptor (ER)␣, ER␤, progesterone receptor (PR), and androgen receptor (AR) mRNA in four primary cultures of HOSE cells obtained from postmenopausal women to those found in late serous adenocarcinoma primary cell cultures and established ovarian cancer cell lines. We observed coexpression of ER␣ and ER␤ mRNA along with AR and PR transcripts in normal HOSE cells and disruption of ER␣ mRNA expression as well as dramatic down-regulation of PR and AR transcript expression in most ovarian cancer cells. In contrast, levels of ER␤ mRNA were unaffected by the malignant state. Additionally, a novel mutation involving a 32-bp deletion in exon 1 of ER␣ transcripts was detected in the SKOV3 cell line. This mutation would explain why SKOV3 was reported to be ER-positive but estrogen-insensitive. Taken together, these findings suggest that estrogens, signaling via either or both ER subtypes, may play an indispensable role in regulating normal HOSE cell functions. Therefore, loss of ER␣, PR, and AR mRNA expression in HOSE cells may be responsible for neoplastic transformation in this cell type. In contrast, the roles played by ER␤ in normal and malignant HOSE cells remain elusive. Finally, the coexistence of mutated ER␣ mRNA and normal ER␤ transcripts in SKOV3 argues in favor of a dependency of ER␤ action on functional ER␣s.

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Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women

Cited by 35 publications

References 7 publications

Prognostic value of progesterone receptor expression in ovarian cancer: a meta-analysis

Prognostic value of progesterone receptor expression in ovarian cancer: a meta-analysis

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Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells

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