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Estrogen Signaling Pathways (estrogen + signaling_pathway)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Estrogen signaling pathway and its imaging in human breast cancer

CANCER SCIENCE, Issue 10 2009
Shin-ichi Hayashi
Recent remarkable progress in hormonal therapy has provided great benefit to breast cancer patients, but it also evokes novel issues: how accurately can the efficacy of each hormonal therapy be predicted and how can hormonal therapy,resistant patients be treated? These clinically important issues must be closely related to the biological events in each cancer, such as the alteration of intracellular multiple estrogen signaling pathways and the estrogen-related cancer microenvironment, which has recently revealed by molecular biological studies on estrogen and its receptors. However, the estrogen signaling status in individual breast cancers has not been clarified yet. Here we present the context of these issues and introduce our study of new tools which enable the visualization of estrogen signals in individual cancers. The assessment of estrogen receptor (ER)-, activity in individual cancers or ER-activating ability of the cancer microenvironment in each breast cancer patient revealed several new findings and interesting observations. We hope that these approaches provide new clues about the estrogen-dependent mechanisms of breast cancer development, and will be useful to advance the diagnosis and treatment of breast cancer patients. (Cancer Sci 2009; 100: 1773,1778) [source]

Genetic engineering to study testicular tumorigenesis

APMIS, Issue 1 2003
WEI YAN
In humans, Sertoli cell tumors account for approximately 4% of all testicular tumors, and 20% of these are malignant. The mechanisms underlying Sertoli cell tumorigenesis remain largely unknown. Using gene knockout technology, we previously generated mutant mice lacking the , subunit of inhibin dimers. The inhibin ,-null male mice develop testicular Sertoli cell tumors with 100% penetrance. These tumors develop as early as 4 weeks of age and cause a cachexia-like wasting syndrome. Castrated inhibin , knockout mice develop sex steroidogenic adrenal cortical tumors. These studies have identified inhibins as secreted tumor suppressors with specificity for the gonads and adrenal glands. It had been suggested that endocrine factors play roles in Sertoli cell tumorigenesis by altering cell cycle machinery of the Sertoli cells. To test the potential of these factors to function as modifiers of Sertoli cell tumorigenesis, we have employed a genetic intercross strategy, breeding inhibin , mutant mice with mutant mice deficient in endocrine signaling factors including gonadotropin releasing hormone (hypogonadal, hpg mice), follicle stimulating hormone, anti-Müllerian hormone (MH), activin receptor type II, or androgen receptor (testicular feminization, tfm mice), or mice overexpressing follistatin. We are also investigating the effects of loss of critical cell cycle regulators, such as cyclin dependent kinase inhibitor p27, on Sertoli cell tumorigenesis in inhibin , knockout males. These studies clearly demonstrate the roles of these factors as modifiers of the Sertoli cell tumorigenesis. Activin signaling through activin receptor type II is responsible for the cachexia-like syndrome observed in the inhibin , knockout mice with tumors. The gonadotropin hormones are essential for testicular tumor development, but elevated FSH levels are not sufficient to cause Sertoli cell tumors. Absence of FSH, lack of androgen receptor, or overexpression of follistatin slows the tumor growth and minimizes the cachexia symptoms, thus prolonging the life span of these double mutant mice. In contrast, absence of AMH or p27 causes earlier onset and more aggressive development of testicular tumor, with an earlier death of double mutant mice. We are currently investigating roles of estrogen signaling pathways, and other cell cycle regulators, in tumor development in the inhibin , knockout mice by generating mice with double or triple mutations. Genetic engineering in mouse models provides a powerful tool to study the mechanisms of testicular tumorigenesis and define the important genetic modifiers in vivo. [source]

Estrogen signaling pathway and its imaging in human breast cancer

Sex-Specific Impact of Aldosterone Receptor Antagonism on Ventricular Remodeling and Gene Expression after Myocardial Infarction

CLINICAL AND TRANSLATIONAL SCIENCE, Issue 2 2009
Ph.D., Rosemeire M. Kanashiro-Takeuchi D.V.M.
Abstract Aldosterone receptor antagonism reduces mortality and improves post-myocardial infarction (Ml) remodeling. Because aldosterone and estrogen signaling pathways interact, we hypothesized that aldosterone blockade is sex-specific. Therefore, we investigated the mpact of eplerenone on left ventricular (LV) remodeling and gene expression of male infarcted rats versus female infarcted rats. Ml and Sham animals were randomized to receive eplerenone (100 mg/kg/day) or placebo 3 days post-surgery for 4 weeks and assessed by echocardiography. In the Ml placebo group, left ventricular end-diastolic dimension (LVEDD) increased from 7.3 ± 0.4 mm to 10.2 ± 1.0 mm (p < 0.05) and ejection fraction (EF) decreased from 82.3 + 4% to 45.5 + 11% (p < 0.05) in both sexes (p= NS between groups). Eplerenone attenuated LVEDD enlargement more effectively in females (8.8 ± 0.2 mm, p < 0.05 vs. placebo) than in males (9.7 ± 0.2 mm, p= NS vs. placebo) and improved EF in females (56.7 ± 3%, p < 0.05 vs. placebo) but not in males (50.6 + 3%, p= NS vs. placebo). Transcriptomic analysis using Rat_230,2.0 microarrays (Affymetrix) revealed that in females 19% of downregu-lated genes and 44% of upregulated genes post-MI were restored to normal by eplerenone. In contrast, eplerenone only restored 4% of overexpressed genes in males. Together, these data suggest that aldosterone blockade reduces Ml-induced cardiac remodeling and phenotypic alterations of gene expression preferentially in females than in males. The use of transcriptomic signatures to detect greater benefit of eplerenone in females has potential implications for personalized medicine. [source]