Estrogen receptor-mediated effects of tamoxifen on human endometrial cancer cells

Sakamoto, Takako; Eguchi, Hidetaka; Omoto, Yoko; Ayabe, Tokiyoshi; Mori, Hiroyuki; Hayashi, Shin Ichi

doi:10.1016/s0303-7207(02)00086-2

Cited by 53 publications

(32 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Estrogen-responsive reporter plasmids pERE (estrogen-responsive element)-Luc (24) were also used in this study. Luciferase assay was done according to a previous report (25) with some modifications. Briefly, 1 Ag of pHRE-Luc or pERE-Luc plasmids and 200 ng of pRL-TK control plasmids (Promega Co., Madison, WI) were used to measure the transcriptional activity of endogenous progesterone receptor or estrogen receptor.…”

Section: Methodsmentioning

confidence: 99%

Progesterone Receptor in Non–Small Cell Lung Cancer—A Potent Prognostic Factor and Possible Target for Endocrine Therapy

Suzuki²,

et al. 2005

Self Cite

View full text Add to dashboard Cite

A possible involvement of gender-dependent factors has been postulated in development of human non-small-cell lung cancers (NSCLC), but its details remain unclear. In this study, we examined biological significance of progesterone receptor in NSCLCs. Progesterone receptor immunoreactivity was detected in 106 of 228 NSCLCs (46.5%). Progesterone receptorpositive NSCLC was frequently detected in female and adenocarcinoma, and was inversely associated with tumornode-metastasis stage and histologic differentiation. Progesterone receptor status was also associated with better clinical outcome of the patients, and a multivariate analysis revealed progesterone receptor status as an independent prognostic factor. Progesterone-synthesizing enzymes were detected in NSCLCs, and tissue concentration of progesterone was higher in these cases (n = 42). Immunoblotting analyses showed the presence of progesterone receptor in three NSCLC cell lines (A549, LCSC#2, and 1-87), but not in RERF-LC-OK or PC3. Transcriptional activities of progesterone receptor were increased by progesterone in these three progesterone receptorpositive NSCLC cells by luciferase assays. Cell proliferation was inhibited by progesterone in these progesterone receptorpositive NSCLC cells in a dose-dependent manner, which was inhibited by progesterone receptor blocker. Proliferation of these tumor cells injected into nude mice was also dosedependently inhibited by progesterone, with a concomitant increase of p21 and p27 and a decrease of cyclin A, cyclin E, and Ki67. Results of our present study suggested that progesterone receptor was a potent prognostic factor in NSCLCs and progesterone inhibited growth of progesterone receptorpositive NSCLC cells. Therefore, progesterone therapy may be clinically effective in suppressing development of progesterone receptor-positive NSCLC patients. (Cancer Res 2005; 65(14): 6450-8)

show abstract

Section: Methodsmentioning

confidence: 99%

Progesterone Receptor in Non–Small Cell Lung Cancer—A Potent Prognostic Factor and Possible Target for Endocrine Therapy

Suzuki²,

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…The luciferase assay was performed according to a previous report (Sakamoto et al 2002) with some modifications. Briefly, we used androgen-responsive reporter plasmids pPSAE-Luc, which contained KLK3 androgen-responsive element (ARE; kindly provided from ASKA Pharmaceutical Co., Ltd), and estrogenresponsive reporter plasmids ptk-estrogen-responsive element (ERE)-Luc, containing Xenopus vitellogenin A2 ERE (Saji et al 2001), in this study.…”

Section: Luciferase Assaymentioning

confidence: 99%

Increased intratumoral androgens in human breast carcinoma following aromatase inhibitor exemestane treatment

Takagi

Miki

Nagasaki³

et al. 2010

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

Sex steroids play important roles in the development of many human breast carcinomas, and aromatase inhibitors are used for the anti-estrogen therapy. Recent studies have demonstrated that aromatase suppressed 5a-dihydrotestosterone (DHT) synthesis in breast carcinoma cells, but intratumoral concentration of androgens and its significance have not been reported in the breast carcinoma patients treated with aromatase inhibitors. Therefore, we examined androgen concentrations in breast carcinoma tissues treated with exemestane, and further performed in vitro studies to characterize the significance of androgen actions. Intratumoral DHT concentration was significantly higher in breast carcinoma tissues following exemestane treatment (nZ9) than those without the therapy (nZ7), and 17b-hydroxysteroid dehydrogenase type 2 (17bHSD2) status was significantly altered to be positive after the treatment. Following in vitro studies showed that 17bHSD2 expression was dose dependently induced by both DHT and exemestane in T-47D breast carcinoma cells, but these inductions were not additive. DHT-mediated induction of 17bHSD2 expression was markedly suppressed by estradiol (E 2 ) in T-47D cells. E 2 -mediated cell proliferation was significantly inhibited by DHT in T-47D cells, associated with an increment of 17bHSD2 expression level. These findings suggest that intratumoral androgen actions are increased during exemestane treatment. 17bHSD2 is a potent DHT-induced gene in human breast carcinoma, and may not only be involved in anti-proliferative effects of DHT on breast carcinoma cells but also serve as a potential marker for response to aromatase inhibitor in the breast carcinoma patients.

show abstract

“…The luciferase assay was performed according to a previous report (Sakamoto et al 2002) with some modifications. Briefly, 1 mg ptk-ERE-Luc plasmids and 200 ng pRL-TK control plasmids were used to measure the transcriptional activity of endogenous ER.…”

Section: Luciferase Assaymentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ in human breast carcinoma: a modulator of estrogenic actions

Suzuki

Hayashi²,

Miki

et al. 2006

Endocr Relat Cancer

View full text Add to dashboard Cite

It has been reported that agonists of peroxisome proliferator-activated receptor g (PPARg) inhibit proliferation of breast carcinoma cells, but the biological significance of PPARg remains undetermined in human breast carcinomas. Therefore, we immunolocalized PPARg in 238 human breast carcinoma tissues. PPARg immunoreactivity was detected in 42% of carcinomas, and was significantly associated with the status of estrogen receptor (ER) a, ERb, progesterone receptor, retinoic X receptors, p21 or p27, and negatively correlated with histological grade or cyclooxygenase-2 status. PPARg immunoreactivity was significantly associated with an improved clinical outcome of breast carcinoma patients by univariate analysis, and multivariate analysis demonstrated that PPARg immunoreactivity was an independent prognostic factor for overall survival in ERa-positive patients. We then examined possible mechanisms of modulation by PPARg on estrogenic actions in MCF-7 breast carcinoma cells. A PPARg activator, 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ), significantly inhibited estrogen-responsive element-dependent transactivation by estradiol in MCF-7 cells, which was blocked by addition of a PPARg antagonist GW9662. Subsequent study, employing a custom-made microarray focused on estrogenresponsive genes, revealed that mRNA expression was significantly regulated by estradiol in 49 genes, but this significance vanished on addition of 15d-PGJ 2 in 16 out of 49 (33%) genes. These findings were confirmed by real-time PCR in 11 genes. 15d-PGJ 2 significantly inhibited estrogenmediated proliferation of MCF-7 cells, and caused accumulation of p21 and p27 protein. These results suggest that PPARg is mainly expressed in well-differentiated and ER-positive breast carcinomas, and modulates estrogenic actions.

show abstract

Estrogen receptor-mediated effects of tamoxifen on human endometrial cancer cells

Cited by 53 publications

References 46 publications

Progesterone Receptor in Non–Small Cell Lung Cancer—A Potent Prognostic Factor and Possible Target for Endocrine Therapy

Progesterone Receptor in Non–Small Cell Lung Cancer—A Potent Prognostic Factor and Possible Target for Endocrine Therapy

Increased intratumoral androgens in human breast carcinoma following aromatase inhibitor exemestane treatment

Peroxisome proliferator-activated receptor γ in human breast carcinoma: a modulator of estrogenic actions

Contact Info

Product

Resources

About