Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality

Pinton, Giulia; Nilsson, Stefan; Moro, Laura

doi:10.1038/s41389-018-0027-9

Cited by 41 publications

(26 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SIRT1 is inversely correlated to ERβ mRNA and protein levels, and the specific ERβ activator KB9520 strongly inhibits SIRT1 mRNA expression. These data collectively support the role of SIRT1 as a tumor promoter in OEC ( 4 ).…”

Section: Ovarian Cancersupporting

confidence: 79%

“…SIRT1 overexpression is reported by many authors as associated with poor outcome and chemoresistance in ovarian cancer of epithelial origin ( 23 – 25 ). Ovarian cells (both normal and tumoral) express two kinds of estrogen receptors (ER), ERα and ERβ which play different roles in cell proliferation and aggressiveness ( 4 ). Specifically, ERα is associated to a poor outcome, while ERβ expression corresponds, on the contrary, to a favorable outcome.…”

Section: Ovarian Cancermentioning

confidence: 99%

“… Mammalian silent information regulator 1 (SIRT1) is reported to play a role in cancers of the secretory organs, including thyroid, pancreatic endocrine, and ovarian tumors [ 1 , 2 , 3 , 4 ]. A recent meta-analysis conducted on 37 selected studies of human cancers analyzed the correlations of overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) with SIRT1 expression [ 5 ].…”

mentioning

confidence: 99%

See 2 more Smart Citations

SIRT1 in Secretory Organ Cancer

Frazzi

2018

Front. Endocrinol.

View full text Add to dashboard Cite

Mammalian silent information regulator 1 (SIRT1) is reported to play a role in cancers of the secretory organs, including thyroid, pancreatic endocrine, and ovarian tumors [1, 2, 3, 4]. A recent meta-analysis conducted on 37 selected studies of human cancers analyzed the correlations of overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) with SIRT1 expression [5]. This study reported that SIRT1 overexpression was associated with a worse OS in liver and lung cancers, while it was not correlated with OS in breast cancer, colorectal cancer, or gastric carcinoma. Collectively, the meta-analysis revealed that an unfavorable OS was associated with SIRT1 expression for solid malignancies. Given the growing importance of this class of lysine/histone deacetylases in human endocrine malignancies, a rational and focused literature assessment is desirable in light of future clinical translations.

show abstract

Section: Ovarian Cancersupporting

confidence: 79%

Section: Ovarian Cancermentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

SIRT1 in Secretory Organ Cancer

Frazzi

2018

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Shuang et al (16) found that SIRT1 could contribute to chemoresistance and the invasive capacity of OC cells, thereby boosting the proliferation of OC. Additionally, silencing of SIRT1 increases the protein expression of estrogen receptor β, which is regarded as an effective inhibitor of OC cells (17). On the other hand, SIRT3 exerts an antitumor effect on the induction of mitochondrial-dependent apoptosis via 5' AMP-activated protein kinase activation in OC cells (18).…”

Section: Introductionmentioning

confidence: 99%

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

Chen

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Ovarian cancer (OC) is the fifth most frequent cause of cancer-associated mortality worldwide, and is accompanied by asymptomatic progression. Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases, comprising seven members (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7). Accumulating evidence has demonstrated that SIRTs act as prognostic estimators in certain types of cancer such as lung cancer, prostate cancer, gastric cancer, breast cancer and colorectal cancer. However, it remains unknown whether individual SIRTs can serve as independent prognostic factors in OC. In the present study, the Kaplan-Meier plotter online database was utilized to examine the prognostic values of SIRT mRNA expression in patients with OC. The results demonstrated that the overexpression of SIRT3, SIRT5, SIRT6 and SIRT7 mRNAs was associated with a good prognosis in patients, whereas elevated mRNA levels of SIRT1 and SIRT4 indicated poor survival in patients with OC. In addition, among the favorable predictors, SIRT3, SIRT5, SIRT6 and SIRT7 overexpression were associated with overall survival (OS), according to clinical characteristics, such as histological classification, clinical stage, pathology grade, drug therapy and tumor protein p53 mutation status in patients with OC. Similarly, SIRT4 mRNA overexpression was associated with poor OS in pathological grade III cancer. High SIRT1 and SIRT4 expression were associated with unfavorable OS at all clinical stages. Furthermore, SIRT1 and SIRT4 were negatively associated with OS in drug-treated patients. In summary, the present study demonstrated that the SIRT family is associated with the prognosis of human OC, suggesting that individual SIRTs may also act as prognostic predictors in patients.

show abstract

“…11 Selective targeting of estrogen receptor α (ERα) with an agonist potentiates chemotherapy for treatment of ovarian cancer, and suppression of SIRT1 may accelerate this therapeutic effect. 12 A high glucose medium can inhibit the effect of many different agents. Testosterone regulates ß-cell mass, at least in part, by androgen receptor (AR) activation in ß-cells of male rats, and the ß-cell AR is degraded under hyperglycemic conditions.…”

mentioning

confidence: 99%

Effects of androgens and estrogens on sirtuin 1 gene expression in human aortic endothelial cells

Tsuchiya

Takei

Tsujikado

et al. 2020

SMJ

View full text Add to dashboard Cite

1 ‫السورتوين‬ ‫تعبير‬ ‫على‬ ‫واالستروجني‬ ‫األندروجينات‬ ‫تأثير‬ ‫دراسة‬ ‫األهداف:‬ .)HAECs(‫البشرية‬ ‫األبهرية‬ ‫البطانية‬ ‫اخلاليا‬ ‫في‬)SIRT1(‫مدار‬ ‫على‬ SIRT-1 ‫لتعبير‬ ‫البلمرة‬ ‫سلسلة‬ ‫تفاعل‬ ‫حتليل‬ ‫أجري‬ ‫املنهجية:‬ ،)DHEA(‫من‬ ‫مختلفة‬ ‫بتركيزات‬ ‫املعاجلة‬ HAECs ‫في‬)h(‫ساعة‬ 48 ‫االستروجني)‬ ‫(هرمون‬)E3(‫و‬)E2(،)E1(‫واالستروجني‬ ‫واألندروجني‬ ‫املرتفع‬ ‫اجللوكوز‬ ‫تأثير‬ ‫كذلك‬ ‫فحصنا‬ ‫الزمنية.‬ ‫الدورات‬ ‫اجلرعة-تبعية‬ ‫لدراسة‬ ‫واإلستروجني.‬ ‫األندروجينات‬ ‫عن‬ ‫الناجم‬ SIRT1 ‫تعبير‬ ‫على‬ ‫وهرمون‬ ‫واالستروجني،‬ ‫واألندروجني‬ ،)DHEA(‫أنتجت‬ ‫النتائج:‬ SIRT1 ‫تعبير‬ ‫في‬ ‫اجلرعة‬ ‫على‬ ‫تعتمد‬ ‫وبزيادة‬ ‫ملحوظ‬ ‫بشكل‬ ‫التستوستيرون‬ ‫ملم)‬ 40(‫املرتفع‬ ‫للجلوكوز‬ ‫كان‬ ‫02ميكروغرام/مل.‬ ‫إلى‬ 10 ‫نطاق‬ ‫في‬ ‫01ميكروغرام/‬ ‫عن‬ ‫الناجت‬ SIRT1 ‫تعبير‬ ‫على‬ ‫ملحوظ‬ ‫بشكل‬ ‫مثبطة‬ ‫تأثيرات‬ ‫زيادة‬ ‫في‬ ،E3 ‫ليس‬ ‫ولكن‬ ، E2 ‫و‬ ‫االستروجني‬ ‫تسبب‬ .)p=0.024(‫مل‬ ‫ميكروغرام/‬ 20 ‫إلى‬ 10 ‫من‬ SIRT1 ‫تعبير‬ ‫في‬ ‫اجلرعة‬ ‫على‬ ‫تعتمد‬ ‫ملحوظة‬ ‫تعبير‬ ‫كبير‬ ‫بشكل‬ ‫مينع‬ ‫لم‬ ‫اجللوكوز‬ ‫من‬ ‫ملم‬ 40 ‫أو‬ ‫ملم‬ 20 ‫مع‬ ‫العالج‬ ‫مل.‬ ‫كال‬ ‫أكد‬ ‫ذلك،‬ ‫ومع‬ ‫التحكم؛‬ ‫وسيط‬ ‫في‬ E3 ‫و‬ E1 ‫عن‬ ‫الناجم‬ SIRT1 E2 ‫عن‬ ‫الناجم‬ SIRT1 ‫تعبير‬ ‫على‬ ‫كبير‬ ‫بشكل‬ ‫للجلوكوز‬ ‫املرتفعني‬ ‫الوسطني‬ ‫التوالي.‬ ‫على‬ ،)p=0.007، p=0.005(‫التحكم‬ ‫وسط‬ ‫في‬ E1 ‫و‬ ‫واالستروجني‬ ‫األندروجني‬ ‫و‬ DHEA ‫أن‬ ‫إلى‬ ‫النتائج‬ ‫هذه‬ ‫تشير‬ ‫اخلالصة:‬ ‫اجللوكوز‬ ‫متوسط‬ ‫إن‬ .HAECs ‫في‬ SIRT1 ‫تعبير‬ ‫بالتأكيد‬ ‫ينشطون‬ E2 ‫و‬ ‫احلد‬ ‫ميكن‬ ‫ال‬ ‫فإنه‬ ، ‫ذلك‬ ‫ومع‬ ‫؛‬ ‫األساسي‬ ‫اجليني‬ ‫التعبير‬ ‫لتثبيط‬ ‫فعال‬ ‫املرتفع‬ .HAECs ‫في‬ ‫قوية‬ ‫واالستروجني‬ ‫األندروجني‬ ‫عن‬ ‫الناجم‬ SIRT1 ‫التعبير‬ ‫من‬ Objectives: To investigate the effect of androgens and estrogens on surtuin 1 (SIRT1) expression in human aortic endothelial cells (HAECs). Methods: Real-time polymerase chain reaction analysis of SIRT-1 expression over 48 hours (h) was performed in HAECs treated with various concentrations of dehydroepiandrostendione (DHEA), androstenedione and testosterone (androgens), estrone (E1), estradiol (E2), and estriol (E3) (estrogens) to investigate the dose-dependency of time courses. The influence of high glucose on SIRT1 expression induced by the androgens and estrogens was also examined. Results: Dehydroepiandrostendione, androstenedione, and testosterone remarkably Original Article produced a dose-dependent increase in SIRT1 expression in the range of 10 to 20 µg/ml. High glucose (40mM) medium had significantly inhibitory effects on 10 µg/ml DHEA-induced SIRT1 expression (p=0.024). Estrone and E2, but not E3, caused a marked dose-dependent increase in SIRT1 expression from 10 to 20 µg/ml. Treatment with 20 mM or 40 mM glucose medium did not significantly inhibit E1and E3-induced SIRT1 expression in control medium; however, both high glucose mediums significantly emphasized E2-induced SIRT1 expression in control medium (p=0.007, p=0.005). Conclusion: These results suggest that DHEA, androstenedione, testosterone, E1, and E2 definitely activate SIRT1 expression in HAECs. A high glucose medium is potent to inhibit the basa...

show abstract

Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality

Cited by 41 publications

References 34 publications

SIRT1 in Secretory Organ Cancer

SIRT1 in Secretory Organ Cancer

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

Effects of androgens and estrogens on sirtuin 1 gene expression in human aortic endothelial cells

Contact Info

Product

Resources

About