 |
|
Researchers may have unlocked the mechanisms that silence the estrogen receptor gene alpha during breast cancer
August 20, 2007The mechanisms that silence the estrogen receptor gene alpha (ER-α) in certain breast cancer cell lines may be closer to being unlocked, according to a study by researchers at Temple University's Sbarro Institute for Cancer Research and Molecular Medicine.
The researchers reported their findings, "Epigenetic Modulation of Estrogen Receptor-α by pRb Family Proteins: A Novel Mechanism in Breast Cancer," in the Aug. 15 issue of the journal Cancer Research (http://cancerres.aacrjournals.org/
cgi/content/abstract/67/16/7731).
In a previous study, the researchers found that in estrogen receptor-positive and estrogen receptor-negative mammary cell lines of women who have been affected with breast cancer, the tumor-suppressing gene pRb2/p130 binds to a specific region of the estrogen receptor gene alpha and forms molecular complexes recruiting and/or interacting with several proteins. They discovered that in estrogen receptor-negative cells - which are able to silence the expression of the estrogen receptor - pRb2/p130 forms a specific molecular complex recruiting a different sequence of proteins than in the estrogen receptor-positive cells.
In the current study, lead by Antonio Giordano, M.D., Ph.D., director of the Sbarro Institute, the researchers showed that the presence of specific pRb2/p130 multimolecular complexes bound to the estrogen receptor gene strongly correlates with the methylation (chemical modification) of the gene.
"Our hypothesis is that the sequence of epigenetic events for establishing and maintaining the silenced state of the estrogen receptor gene alpha during the breast cancer progression is mediated by pRb2/p130 in association with specific proteins that modified the DNA structure through specific mechanisms," said Giordano, who discovered the Rb2 gene while working at Temple's Fels Cancer Institute in the early 1990s.
"In other words, the presence of a specific pRb2/p130 multimolecular complex may dictate a local change of the DNA structure of the estrogen receptor alpha gene and influence its susceptibility to chemical modification (DNA methylation), as well as to different epigenetic alterations leading to estrogen receptor alpha silencing," added Marcella Macaluso, research assistant professor at the Sbarro Institute and the study's lead author.
Giordano says this study provides a basis for understanding how the complex pattern of estrogen receptor gene alpha methylation and transcriptional silencing is generated, as well as for understanding the relationship between this pattern and its function during breast cancer progression.
By understanding this mechanism of how pRb2/p130 recruits molecules, he says, researchers will be able to design therapies and drugs that are very precise in the target they recognize.
"One gene on its own doesn't mean anything," he explains. "It's the dialogue among the genes that are writing the sentences, and this finding really writes a very important sentence in the book that we are authoring on uncovering the understanding of how a normal cell functions and why some therapies work or some therapies don't work. It also clearly shows that cancer is not the event of one gene, but an army of genes and it looks like pRb2/p130 is one of the generals."
Giordano and Macaluso were joined in this study by research fellow Micaela Montanari and doctoral students Paul Bart Noto and Valter Gregorio from the Sbarro Institute, and Professor Christian Bronner from the Centre National de la Recherche Scientifique/Université Louis Pasteur in France.
The study was coordinated by Giordano and carried out at Temple's Sbarro Institute and the Department of Human Pathology and Oncology at the University of Siena in Italy. It was funded by the National Institutes of Health, the U.S. Army Medical Research and Material Command and the Sbarro Health Research Organization.
Temple University
In the current study, lead by Antonio Giordano, M.D., Ph.D., director of the Sbarro Institute, the researchers showed that the presence of specific pRb2/p130 multimolecular complexes bound to the estrogen receptor gene strongly correlates with the methylation (chemical modification) of the gene.
"Our hypothesis is that the sequence of epigenetic events for establishing and maintaining the silenced state of the estrogen receptor gene alpha during the breast cancer progression is mediated by pRb2/p130 in association with specific proteins that modified the DNA structure through specific mechanisms," said Giordano, who discovered the Rb2 gene while working at Temple's Fels Cancer Institute in the early 1990s.
"In other words, the presence of a specific pRb2/p130 multimolecular complex may dictate a local change of the DNA structure of the estrogen receptor alpha gene and influence its susceptibility to chemical modification (DNA methylation), as well as to different epigenetic alterations leading to estrogen receptor alpha silencing," added Marcella Macaluso, research assistant professor at the Sbarro Institute and the study's lead author.
Giordano says this study provides a basis for understanding how the complex pattern of estrogen receptor gene alpha methylation and transcriptional silencing is generated, as well as for understanding the relationship between this pattern and its function during breast cancer progression.
By understanding this mechanism of how pRb2/p130 recruits molecules, he says, researchers will be able to design therapies and drugs that are very precise in the target they recognize.
"One gene on its own doesn't mean anything," he explains. "It's the dialogue among the genes that are writing the sentences, and this finding really writes a very important sentence in the book that we are authoring on uncovering the understanding of how a normal cell functions and why some therapies work or some therapies don't work. It also clearly shows that cancer is not the event of one gene, but an army of genes and it looks like pRb2/p130 is one of the generals."
Giordano and Macaluso were joined in this study by research fellow Micaela Montanari and doctoral students Paul Bart Noto and Valter Gregorio from the Sbarro Institute, and Professor Christian Bronner from the Centre National de la Recherche Scientifique/Université Louis Pasteur in France.
The study was coordinated by Giordano and carried out at Temple's Sbarro Institute and the Department of Human Pathology and Oncology at the University of Siena in Italy. It was funded by the National Institutes of Health, the U.S. Army Medical Research and Material Command and the Sbarro Health Research Organization.
Temple University
Estrogen Current Events and Estrogen News RSSMenopause-cardiology consensus statement on cardiovascular disease and on HRT
A menopause-cardiology consensus statement has called for direct action to prevent cardiovascular disease (CVD) in menopausal women. The statement also concludes that there is little evidence of increased CVD risk in taking HRT.
Heart and bone damage from low vitamin D tied to declines in sex hormones
Researchers at Johns Hopkins are reporting what is believed to be the first conclusive evidence in men that the long-term ill effects of vitamin D deficiency are amplified by lower levels of the key sex hormone estrogen, but not testosterone.
Fertility procedures need not delay breast cancer treatment for younger women
A new study published in the November issue of the Journal of the American College of Surgeons shows that breast cancer patients under 40 years old who undergo fertility preservation do not face a significant delay in the treatment of their disease when their care is coordinated in a timely fashion.
Coffee break: Compound brewing new research in colon, breast cancer
A compound in coffee has been found to be estrogenic in studies by Texas AgriLife Research scientists.
Mayo researchers find robotic repair for vaginal prolapse has significant benefits
New Mayo Clinic research has found that robotic surgery for vaginal prolapse dramatically reduces patient hospital stay and recovery time.
Estrogen therapy likely must be given soon after menopause to provide stroke protection
For estrogen replacement to provide stroke protection, it likely must be given soon after levels drop because of menopause or surgical removal of the ovaries, scientists report in the Journal of Neuroscience.
Oral contraceptives may benefit women with asthma
New research shows that during natural menstrual cycles, women with asthma who were not taking oral contraceptives (OC) had lower exhaled nitric oxide levels (eNO), a marker of airway inflammation associated with asthma, than women who were taking OC.
Study shows hormone replacement therapy decreases mortality in younger postmenopausal woman
Hormone replacement therapy (HRT) to treat menopausal estrogen deficiency has been in widespread use for over 60 years. Several observational studies over the years showed that HRT use by younger postmenopausal women was associated with a significant reduction in total mortality; available evidence supported the routine use of HRT to increase longevity in postmenopausal women.
Hormone mix could cut breast cancer risk and treat symptoms of menopause
The right combination of estrogen and a selective estrogen receptor modulator (SERM), which blocks the effects of estrogen in breast tissue, could relieve menopause symptoms and cut breast cancer risk.
Breast tenderness during hormone replacement therapy linked to elevated cancer risk
Women who developed new-onset breast tenderness after starting estrogen plus progestin hormone replacement therapy were at significantly higher risk for developing breast cancer than women on the combination therapy who didn't experience such tenderness, according to a new UCLA study.
More Estrogen Current Events and Estrogen News Articles
|
Source Naturals Phyto-Estrogen Cream, 4 oz (113.4 g) by Source Naturals Advanced liposomal delivery. Non-GMO soy. Phyto-Estrogen Cream offers some of the finest phytoestregens, renowned for use during menopause. Each ounce contains 60 mg of isoflavone phytoestrogens, along with 150 mg of pomegranate juice extract, and 100 mg of red clover extract. Micro-penetrating liposomes pass through skin layers more easily than non-liposomal creams. | |
 |
Natural Estrogen with Pomegranate Extract, 60 caplets by Life Extension Natural Estrogen with Pomegranate Extract60 caplets Item Catalog Number: 712 In an attempt to provide aging women with the multiple health effects of the bodies’ estrogen without side effects, scientists have discovered plant extracts with estrogenic activity (phytoestrogens). Natural Estrogen with Pomegranate Extract is one answer to the concerns of maintaining healthy hormone function. A review of the published literature reveals some interesting findings about how plant-derived estrogens can provide safe and effective support for such menopausal symptoms as hot flashes. Derived from organically-grown fruit, the pomegranate extract in this formula has the same ratio of polyphenols found in the whole fruit and all the benefits one would get from the juice without the sugar, calories,... |
 |
Estrogen/Estriol (Bio-Identical) Fragrance Free Cream 2 oz. Pump Bottle by Radiant Laboratories - Made In USA Paraben-Free and Unscented. Menopausal Hot Flashes? Night Sweats? Trouble Sleeping? Replenish Your Estrogen Naturally and Safely. Get your life back! Estriol Has Been Used in Europe for Years. Bio-identical Hormones Are Safe and Effective. Non Prescription Bio-identical Natural Estrogen (Estriol Usp) Not to Be Confused with Phyto-estrogens. Bio-identical Hormones Are Safe for Women Help Relieve Menopause Symptoms. Estriol is not a phyto estrogen. Don't confuse phyto estrogens with pure natural estriol USP. The natural estrogen, estriol USP, is made the same way natural progesterone USP is made. Sterol analogues found in many varieties of plants are combined with specific bacteria and the resulting hormone is bio identical in chemical structure to the hormone produced by the human body.... |
 |
Emerita Phytoestrogen Body Cream with Black Cohosh, 2-Ounce Tube by Emerita Peri/Menopause support. Paraben-free. Who knew a little tube of cream could change the world? In 1978 we had a revolutionary idea: that there was not enough real choice when it came to peri / menopause. So we created Pro-Gest, Phytoestrogen Cream and Pers |
 |
Estrogen Revisited: Lifelong & Fearless by Donna Walters (Author) Estrogen is essential for good health and well being in women of all ages throughout their lives. I have written this book because I want to encourage women who have been on hormone replacement, like me, to consider remaining on it for life as I plan to do. For women who have been scared or hesitant to take estrogen because they are afraid of contracting breast cancer as predicted by the incorrect conclusions of the Women's Health Initiative in 2002, read this book and save your life. My doctor told me that I should stop taking estrogen because it is recommended for the shortest amount of time to control symptoms only. I have researched this issue for over a year because I want to make the right decision for me. I have decided to share my findings and experience of long term estrogen use... |
 |
Phyto-Estrogen 60 Capsules by Gaia Herbs Provides a Natural Hormonal Balance During the Onset of Menopause Rich Natural Source of Phytoestrogens Support for the Peri-Menopause and Menopausal Years |
 |
Estroven Maximum Strength - 98 Caplets by Amerifit Estroven Maximum Strength is clinically shown to reduce hot flashes and night sweats. It contains a higher level of the key black cohosh and soy isoflavones ingredients found in Estroven Regular Strength, plus additional vitamins and minerals for women's health. |
 |
Alternative Health & Herbs Remedies Female Estrogen W, progesterone, 1-Ounce Bottle by Alternative Health & Herbs Remedies Alternative Health & Herbs Remedies Female Estrogen W, progesterone, promotes hormonal balance, effective for women who are experiencing menopause and it does not contain hormones. |
 |
TestroPlex - 90 Capsules Anti-Estrogen & Anti-Aromatase Complex Testosterone Booster Tribulus Chrysin by Bionutricals The amount of free testosterone can be altered (increased) by the use of aromatase inhibitors such as TestroPlexTM. The less testosterone that is synthesized [aromatized] into estrogen, the more total testosterone) or inhibitors of the plasma proteins that bind into testosterone. Manipulating the tendency of a testosterone to exist in an unbound state is an effective way to alter the overall activity and potency of ones overall testosterone levels. Higher levels of testosterone produce an enhanced anti-glucocorticoid effect, which yields an anti-catabolic, or more precisely, anti-proteoolytic, effect on muscle cells. This indirect effect is the result of testosterones high affinity for binding with glucocorticoid receptors, thus blocking the normal messenger pathway that triggers protein... |
 |
The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth, Second Edition by Barbara Seaman (Author) A Library Journal Best Consumer Health Book of 2003 and an American Library Association/Booklist Editor's Choice Book of 2003 "Barbara Seaman is the first prophet of the women's health movement and her prophecies are still coming true."-Gloria Steinem "A wake-up call to women about unquestioningly accepting doctors' orders."-Booklist (starred review) "Lively and impassioned . . . [Seaman] certainly makes her point."-Gina Kolata, The New York Times With the ardent tone of a close friend, Barbara Seaman draws on forty years of journalistic research to expose the "menopause industry" and shows how estrogen therapy often causes more problems-including breast cancer, heart attack, and stroke-than it cures. The Greatest Experiment Ever Performed on Women tracks the... |
| © 2009 BrightSurf.com |