Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus

Ivanova, Margarita; Radde, Brandie N.; Son, Jieun; Mehta, Fabiola F.; Chung, Sang-Hyuk; Klinge, Carolyn M.

doi:10.1530/jme-13-0051

Cited by 19 publications

(11 citation statements)

References 57 publications

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“…Beside ovarian cancer, TFAM upregulation is also observed in breast, colorectal, bladder, endometrial and arsenic induced skin cancer with subsequent increase in MtBIO and cellular proliferation. Many study show similar results both in experimental and clinical settings [71][72][73][74][75][76][77]. Such findings suggest TFAM as one of the most important therapeutic targets in chemoresistant ovarian cancer.…”

Section: Mitochondrial Transcription Factor a (Tfam)supporting

confidence: 62%

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Uddin¹,

Kim²,

Suh³

et al. 2014

J Cancer Sci Ther

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IntroductionOvarian cancer is the most lethal gynecologic malignancy worldwide typically in the post-menopausal women and 5 th leading cause of death in the United States [1][2][3]. About 80% of women are diagnosed at the advanced-stage of disease and have poor prognosis. The 5-year overall survival rate is 45% or below [4][5][6]. Despite the first complete response after the front-line platinum-based chemotherapeutic drugs [7,8], approximately 25% patients suffer from relapse within 6 months who are thought, by definition, to have a chemoresistance [9][10][11][12]. Combination of platinum and other drugs might improve the survival rate [13], but is not out of the danger of additive toxicity [14].Several genetic alterations have been observed in ovarian cancer, involving deactivation mutations in tumor suppressor genes, such as p53, BRCA1 and BRCA2, and activation mutation and/or amplification of proto-oncogenes, like c-MYC, KRAS and AKT [15]. Recent genomic analysis of The Cancer Genome Atlas reported mutations in p53 gene in 96% of 316 cases of high-grade ovarian serous carcinoma (HGOSC) [16]. Other important genetic changes affect phosphatidyinositol-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) cascade. The mTOR plays a central role in energy metabolism, cell growth/division through macromolecular synthesis and is found to be activated in ovarian cancer [6], which indicates a close relationship between genetic alteration and energy metabolism. It was observed that hexokinase (HK) II, the rate limiting initial enzyme in glycolysis, is overexpressed in ovarian cancer [12]. The genetic alterations and subsequent metabolic remodeling have been found to be associated with the chemoresistance [17], such as association of rictor (mTORC2 component) with resistance to cisplatin [2]. Cisplatin-induced caspase activation causing PTEN cleavage has also been reported as a potential mechanism of chemoresistance in ovarian cancer [18].Mitochondria is a well-adapted endosymbiotic intracellular organelles, became efficient for energy production through-out the course of evolution [19]. They are critical for survival and proliferation of living organisms under aerobic conditions and produce ATP through oxidative phosphorylation (OXPHOS) [20]. Beyond the conventional function they have crucial role in certain neurodegenerative diseases and cancer [21][22][23]. Cellular proliferation largely depends on mitochondrial amount, governed by the process of MtBIO [20]. MtBIO is the production of daughter mitochondria usually from previously existed one through a division process of called fission, subsequent growth, and maintenance by fusion and autophagy of mitochondria (mitophagy) [24]. Currently it has been observed that MtBIO is associated with cancer chemoresistance [25,26] through the modulation of associated proteins such as methylation-controlled J-protein (MCJ, also known as DNAJC15) [25,27], prohibitin 1 (PHB-1) [28][29][30], myeloid cell leukemia sequence 1 (MCL-1) [31,32] etc. in ovarian cancer. Thus it can be s...

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Section: Mitochondrial Transcription Factor a (Tfam)supporting

confidence: 62%

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Uddin¹,

Kim²,

Suh³

et al. 2014

J Cancer Sci Ther

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“…Estrogens have been reported to exert direct and indirect effects on mitochondrial function, and co-localization of ERα and/or ERβ with the mitochondria has been reported (52). Estrogens can regulate mitochondrial morphology, biogenesis, bioenergetics and mitochondrial genome transcription, among other functions, in a cell-specific manner (54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

Effects of 60�kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression

et al. 2018

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Estrogens and estrogen receptors (ERs), such as ERα and ERβ, prolactin (PRL) and prolactin receptor (PRLR) have been reported to be involved in the physiopathology of uterine cervical cancer (UCC). The 60 kDa PRL is an isoform of PRL, which is produced by UCC-derived cells. The present study aimed to evaluate the expression of hormonal receptors in different degrees of cervical lesions, and to determine whether 60 kDa PRL and 17β-estradiol (E2) modulated cell survival and metabolism in UCC cells, and in HaCaT cells transduced with human papillomavirus (HPV) 16 and 18 E6/E7 oncogenes. ERα, ERβ, PRLR, Ki67 and B-cell lymphoma 2 expression levels were analyzed in biopsies of precursor lesions and UCC using immunohistochemistry. In addition, HeLa, SiHa and C33A cells, and transduced HaCaT cells, were stimulated with 60 kDa PRL, E2 or a combination of both. Proliferation was evaluated using the xCELLigence platform, apoptosis was analyzed by flow cytometry and cell metabolism was determined using the MTT assay. The results revealed that ERα, ERβ, PRLR and Ki67 expression levels were increased during the progression of cancer. In vitro, 60 kDa PRL alone significantly increased proliferation of SiHa cells. Furthermore, E2 alone or in combination with 60 kDa PRL increased the sensitivity of SiHa cells to cisplatin and increased the percentage of apoptosis; in HaCaT cells, these treatment strategies had the opposite effect on cisplatin sensitivity. Treatment with E2 increased mitochondrial activity in HeLa and SiHa cells, and in HaCaT cells transduced with HPV 16 E6/E7 and HPV 18 E6 oncogenes. PRL had a similar effect on HeLa cells, and on HaCaT cells transduced with HPV 18 E6 and HPV 16 E7. The co-expression of these receptors demonstrated the hormonal dependence of UCC. In addition, E2 and the 60 kDa PRL significantly impacted the metabolism, but not the survival, of cells.

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“…Estrogen treatment also modulates the apoE receptor LDL related receptor protein (LRP1) (148). Estrogen treatment in ovariectomized mice also causes increases in LRP, an apoE binding protein, in the hippocampus and neocortex (149). Along these lines, apoE synthesis is required for estrogen-induced neuroprotection and neurite outgrowth (148, 150, 151) and is lost in the presence of ɛ4 (151).…”

Section: Sex Differences In Apoe Genotype and Risk Of Alzheimer’smentioning

confidence: 99%

Age, APOE and sex: Triad of risk of Alzheimer’s disease

Riedel

Thompson

Brinton

2016

The Journal of Steroid Biochemistry and Molecular Biology

485

400

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Age, apolipoprotein E ɛ4 (APOE) and chromosomal sex are well-established risk factors for late-onset Alzheimer’s disease (LOAD; AD). Over 60% of persons with AD harbor at least one APOE-ɛ4 allele. The sex-based prevalence of AD is well documented with over 60% of persons with AD being female. Evidence indicates that the APOE-ɛ4 risk for AD is greater in women than men, which is particularly evident in heterozygous women carrying one APOE-ɛ4 allele. Paradoxically, men homozygous for APOE-ɛ4 are reported to be at greater risk for mild cognitive impairment and AD. Herein, we discuss the complex interplay between the three greatest risk factors for Alzheimer’s disease, age, APOE-ɛ4 genotype and female sex. We propose that the convergence of these three risk factors, and specifically the bioenergetic aging perimenopause to menopause transition unique to the female, creates a risk profile for AD unique to the female. Further, we discuss the unique risk of the APOE4 positive male which appears to emerge early in the aging process. Evidence for impact of the triad of AD risk factors is most evident in the temporal trajectory of AD progression and burden of pathology in relation to APOE genotype, age and sex. Collectively, the data indicate complex interactions between age, APOE genotype and gender that belies a one size fits all approach and argues for a precision medicine approach that integrates across the three main risk factors for Alzheimer’s disease.

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Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus

Cited by 19 publications

References 57 publications

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Effects of 60�kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression

Age, APOE and sex: Triad of risk of Alzheimer’s disease

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