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:4/19/2016)... , UAE, April 20, 2016 ... implemented as a compact web-based "all-in-one" system solution for ... biometric fingerprint reader or the door interface with integration ... modern access control systems. The minimal dimensions of the ... readers into the building installations offer considerable freedom of ...
(Date:4/13/2016)... -- IMPOWER physicians supporting Medicaid patients in Central ... in telehealth thanks to a new partnership with higi. ... patients can routinely track key health measurements, such as ... when they opt in, share them with IMPOWER clinicians ... retail location at no cost. By leveraging this data, ...
(Date:3/23/2016)... 2016 Einzigartige ... und Stimmerkennung mit Passwörtern     ... MESG ), ein führender Anbieter digitaler Kommunikationsdienste, ... SpeechPro zusammenarbeitet, um erstmals dessen Biometrietechnologie einzusetzen. ... Möglichkeit angeboten, im Rahmen mobiler Apps neben ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... UAS LifeSciences, one of ... their brand, UP4™ Probiotics, into Target stores nationwide. The company, which has been ... Target to its list of well-respected retailers. This list includes such fine stores ...
(Date:6/23/2016)... TORONTO , June 23, 2016 /PRNewswire/ - ... Ontario biotechnology company, Propellon ... the development and commercialization of a portfolio of ... cancers. Epigenetic targets such as WDR5 represent an ... contribute significantly in precision medicine for cancer patients. ...
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... -- The Prostate Cancer Foundation (PCF) is pleased to announce 24 new ... prostate cancer. Members of the Class of 2016 were selected from a pool ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
Breaking Biology Technology: