Navigation Links
Plasticity of hormonal response permits rapid gene expression reprogramming
Date:5/15/2011

Gene expression is the process of converting the genetic information encoded in DNA into a final gene product such as a protein or any of several types of RNA. Scientists have long thought that the gene programs regulated by different physiological processes throughout the body are robustly pre-determined and relatively fixed for every specialized cell. But a new study by researchers from the University of California, San Diego School of Medicine reveals the unsuspected plasticity of some of these gene expression programs.

Their findings, to be published in the May 15 advanced on-line edition of journal Nature, show the existence of distinct regulated gene programs that can be alternatively induced, depending on the intracellular conditions. The study helps explain why, for example, the same signaling event such as cellular response to circulating hormones in the human body can be beneficial for normal development, but also becomes cancerous when combined with other genetic lesions.

The UCSD scientists found that the response to the hormone androgen in prostatic epithelial cells can be subject to dramatic reprogramming events that lead to alternative gene programs and profiles. They suggest that this plasticity could be the basis for development and progression of at least some forms of cancer, as well as for cell differentiation during development.

From a patient perspective, the results of this study may explain how hormonal therapy, applied to prostate cancer patients to block the pre-established, hormone-regulated tumor growth, escapes this treatment in a more malignant way.

"Aggressive cell types, such as those found in prostate cancer, basically learn to ignore the hormone therapy," said co-principal investigator Xiang-Dong Fu, PhD, professor in the UCSD Department of Cellular and Molecular Medicine, who collaborated with co-principal investigator Michael G. Rosenfeld, MD, professor in the UCSD Department of Medicine and a Howard Hughes Medical Institute investigator.

In this study, the UCSD researchers looked at the down-regulation in expression of a single transcription factor, FoxA1, an unfavorable sign in certain advanced prostate tumors. They present evidence that FoxA1, which is needed for normal prostatic development, can simultaneously facilitate and restrict the genomic binding of the receptor that controls the hormonal response. Consequently, down-regulation of FoxA1 triggers reprogramming of the hormonal response.

Interestingly, other cancer-associated events, such as specific AR genetic mutations, appear capable of inducing a similar effect. The subsequent massive switch in AR binding to a distinct cohort of pre-established regulatory elements in the human genome (called enhancers) is what may allow the cancer cells to "reprogram" themselves.

These findings suggest that therapies designed to stop the switch between different alternative gene programs may be more effective than simply blocking the hormonal response, according to co-first author Dong Wang, PhD and co-first author and co-principal investigator Ivan Garcia-Bassets, PhD, research assistant professor in the UCSD Division of Endocrinology and Metabolism, Department of Medicine.


'/>"/>

Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related biology news :

1. Astrocytes and synaptic plasticity
2. Protein linked to mental retardation controls synapse maturation, plasticity, CSHL team finds
3. Ritalin boosts learning by increasing brain plasticity
4. New period of brain plasticity created with transplanted embryonic cells
5. Plasticity of plants helps them adapt to climate change
6. Breast cancer cells recycle to escape death by hormonal therapy
7. Major NSF grant boosts UNH research on hormonal genomics
8. The pill for him: Scientists find a hormonal on-and-off switch for male fertility
9. Soy germ-based supplement SE5-OH containing natural S-Equol examined for safety, hormonal influence
10. Hormonal contraceptives associated with higher risk of female sexual dysfunction
11. U of A researcher questions whether genius might be a result of hormonal influences
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/12/2016)... 2016 WearablesResearch.com , a brand of ... results from the Q1 wave of its quarterly wearables ... consumers, receptivity to a program where they would receive ... insurance company. "We were surprised to see ... Michael LaColla , CEO of Troubadour Research, "primarily because ...
(Date:4/28/2016)... April 28, 2016 First quarter 2016:   ... 966% compared with the first quarter of 2015 The ... 589.1 M (loss: 18.8) and the operating margin was 40% (-13) ... Cash flow from operations was SEK 249.9 M (21.2) ... guidance is unchanged, SEK 7,000-8,500 M. The operating margin ...
(Date:4/15/2016)... CHICAGO , April 15, 2016  A ... companies make more accurate underwriting decisions in a ... offering timely, competitively priced and high-value life insurance ... health screenings. With Force Diagnostics, rapid ... and lifestyle data readings (blood pressure, weight, pulse, ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... , ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical ... mesothelioma. Their findings are the subject of a new article on the Surviving Mesothelioma ... in the blood, lung fluid or tissue of mesothelioma patients that can help point ...
(Date:6/23/2016)... Md. , June 23, 2016 A person ... from the crime scene to track the criminal down. ... the U.S. Food and Drug Administration (FDA) uses DNA evidence ... Sound far-fetched? It,s not. The FDA ... sequencing to support investigations of foodborne illnesses. Put as simply ...
(Date:6/23/2016)... 23, 2016   EpiBiome , a precision microbiome ... in debt financing from Silicon Valley Bank (SVB). The ... to advance its drug development efforts, as well as ... "SVB has been an incredible strategic partner to ... traditional bank would provide," said Dr. Aeron Tynes ...
(Date:6/23/2016)... NEWPORT BEACH, Calif. , June 23, 2016 /PRNewswire/ ... offering new biological discoveries to the medical community, has ... and co-founder Matthew Nunez . "We ... provide us with the capital we need to meet ... funding will essentially provide us the runway to complete ...
Breaking Biology Technology: