Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma

Miyamoto, Tomoyuki; Watanabe, Jun; Hata, Hiroki; Jobo, Toshiko; Kawaguchi, Miwa; Hattori, Manabu; Saito, Mayumi; Kuramoto, Hiroyuki

doi:10.1016/j.jsbmb.2004.07.007

Cited by 53 publications

(44 citation statements)

References 34 publications

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“…Several studies have demonstrated that PRB was more common than PRA in endometrial carcinoma [53,54]. Very recently, we reported that cases negative for either one or both of the PR isoforms were associated significantly with shorter disease-free and overall survival of the patients [54].…”

Section: ) Progesterone Receptorsmentioning

confidence: 75%

Biological Roles of Estrogen and Progesterone in Human Endometrial Carcinoma - New developments in potential endocrine therapy for endometrial cancer -

et al. 2007

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Abstract. Endometrial carcinoma is one of the most common female pelvic malignancies. It is well known that uterine endometrial cell proliferation is under the control of both estrogen and progesterone. In this review, results of the recent studies on the biosynthesis and action of estrogen and progestin in normal endometrium and its disorders will be summarized and the new aspects of hormonal therapies in the patients with endometrial carcinoma will be discussed including its future prospectives. We reported that the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are markedly different between human breast and endometrial carcinoma, although both of them are considered "estrogen-dependent malignancies". In addition, the biological significance of Progesterone receptor (PR) isoforms is considered to differ between endometrial and breast carcinomas. Clinical data concerning Hormone replacement therapy (HRT) and estrogen-dependent cancer risk also support these findings. These basic and clinical findings help to understand the biology and provide the new knowledge for prevention, diagnosis and treatment of human endomerial carcinoma. Specific endocrine treatment of endometrial carcinoma should be explored in future, although aromatase inhibitors are the most effective endocrine treatments of estrogen-responsive breast carcinoma. Retinoid, metabolities of vitamin A, and synthetic peroxisome proliferator-activated receptor (PPAR) γ ligands, which have been used for the treatment of insulin resistance in type II diabetes mellitus, may be the important candidates as drugs not only for prevention but also for possible endocrine treatment of endometrial carcinoma.

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Section: ) Progesterone Receptorsmentioning

confidence: 75%

Biological Roles of Estrogen and Progesterone in Human Endometrial Carcinoma - New developments in potential endocrine therapy for endometrial cancer -

et al. 2007

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“…It has been reported that progesterone-inhibited cell growth and invasiveness may occur mainly through PRB. Moreover, a drastic decrease of PRB reflects poor prognosis in endometrial cancer patients (17)(18)(19). The relative expression level of the ER and PR isoforms may be a key determinant of cellular responses to endocrine treatment.…”

Section: Discussionmentioning

confidence: 99%

Response-specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long-term exposure to medroxyprogesterone acetate

Zhao

et al. 2012

Oncology Letters

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Abstract. Progestins, particularly medroxyprogesterone acetate (MPA), have for a long time been used as conservative treatment for young patients with clinical stage I, grade I endometrial carcinoma. However, more than 30% of patients with endometrial adenocarcinoma display resistance to endocrine therapies at the time of presentation and most cancer patients that initially respond to progestin treatment will at some point develop resistance, resulting in tumor progression. The cellular mechanisms underlying acquired resistance to progestin are poorly understood. In order to investigate the molecular mechanisms whereby human endometrial adenocarcinoma develops resistance to progestin therapy, we have undertaken to develop human endometrial adenocarcinoma cell lines that are resistant to the growth-inhibitory effects of progestins in vitro. A progestin-resistant subcell line of Ishikawa cells was developed from Ishikawa human endometrial adenocarcinoma cells by stepwise selection in increasing concentrations of the synthetic progestin, MPA, over ten months. The doubling time of the progestin-resistant cells (34.18±3.15 h) grown routinely in the medium containing 10 µM MPA was not significantly different from the doubling time of the parent Ishikawa cells (35.14±2.68 h) grown in the absence of MPA (t=-0.331, P=0.762). Moreover, the effect of treatment with MPA shifted from suppression of growth and invasiveness, as observed in the parent Ishikawa cells, to stimulation of growth and invasiveness in the progestin-resistant Ishikawa cells. The positive rates of estrogen receptor a (ERα) and progesterone receptor B (PRB) of the progestin-resistant Ishikawa cells were significantly reduced, whilst the positive rate of ERβ was significantly enhanced compared to the parent Ishikawa cells. These differences were statistically significant (P<0.05). Our results indicate that long-term treatment with MPA in Ishikawa cells may give rise to a resistance effect to MPA. When the resistant subtype is acquired, treatment with MPA enhances cancer cell proliferation and invasiveness. The imbalance of ER and PR subtypes may contribute to the mechanisms involved in progestin resistance. Determination of the subtypes of ER and PR may provide important additional information on the hormone sensitivity of endometrial carcinoma.

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“…Several studies have demonstrated that PRB was more common than PRA in endometrial carcinoma (Miyamoto et al 2004;Saito et al 2006) (Fig. 2).…”

Section: Progesterone Receptormentioning

confidence: 97%

Hormone Replacement Therapy and Cancers: The Biological Roles of Estrogen and Progestin in Tumorigenesis are Different between the Endometrium and Breast

Itō

2007

Tohoku J. Exp. Med.

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Hormone replacement therapy (HRT) has become available over the past few decades, but the risk of breast cancer with HRT remains controversial. The Women's Health Initiative Study has recently demonstrated that women receiving estrogen plus progestin (HRT) have an increased risk of invasive breast carcinoma, although women receiving estrogen alone (estrogen replacement therapy) exhibit no increased risk of breast carcinoma. By contrast, the risk of endometrial carcinoma increases with estrogen replacement therapy, while HRT reduces the risk of endometrial carcinoma. These clinical findings suggest that the biological roles of estrogen and progestin in tumorigenesis are certainly different between the endometrium and breast, although both are considered "estrogen-dependent tissues". In this review, I summarize the recent studies and indicate that the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are markedly different between human breast and endometrial carcinomas. 17β -hydroxysteroid dehydrogenases (17-HSDs) are enzymes estrogen replacement therapyinvolved in the formation of active sex steroids. Estrogens are interconverted by two enzymes, 17-HSD types 1 and 2. Type 1 converts estrone to estradiol, and type 2 catalyzes the reverse reaction. 17-HSD type 5 reduces androstenedione to testosterone. 17-HSD type 1 plays an important role in the regulation of high estradiol levels in breast carcinoma tissues, whereas 17-HSD types 2 and 5 appear to be essential for the maintenance of estradiol concentrations in endometrial carcinoma tissues. In addition, the biological significance of progesterone receptor isoforms differs between endometrial and breast carcinomas. These findings may provide new insights into the biology of "estrogendependent tissues". hormone replacement therapy (HRT); 17β -hydroxysteroid dehydrogenases; estrogen; progesterone; breast carcinoma; endometrial carcinoma

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Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma

Cited by 53 publications

References 34 publications

Biological Roles of Estrogen and Progesterone in Human Endometrial Carcinoma - New developments in potential endocrine therapy for endometrial cancer -

Biological Roles of Estrogen and Progesterone in Human Endometrial Carcinoma - New developments in potential endocrine therapy for endometrial cancer -

Response-specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long-term exposure to medroxyprogesterone acetate

Hormone Replacement Therapy and Cancers: The Biological Roles of Estrogen and Progestin in Tumorigenesis are Different between the Endometrium and Breast

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