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

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.


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

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