TITLE: Evaluation of Androgen Receptor Function in Prostate Cancer Prognosis and Therapeutic Stratification PRINCIPAL INVESTIGATOR:
نویسندگان
چکیده
half of all prostate cancers in the Western countries harbor gene fusions that involve regulatory sequences of the androgen receptor (AR)-responsive genes (predominantly TMPRSS2) and protein coding sequences of nuclear transcription factors of the ETS gene family (predominantly ERG). This leads to unscheduled androgen-dependent expression ofETS-related transcription factors in tumor cell-specific manner. Extensive evaluations of ERG alterations at genome, transcript, and protein levels demonstrate unprecedented specificity of ERG for detecting prostate tumor cells. Assessment of ERG alterations in combination with other common prostate cancer gene alterations (AMACR, PCA3, p63) has potential in improving CaP diagnosis. Utility of ERG in assessing the clinical behavior of prostate cancer is uncertain. Strong correlation of ERG expression with known androgen-responsive genes in prostate tumors has potential in developing gene panels inclusive of ERG for monitoring androgen receptor functional status in the disease continuum. Studies focusing on oncogenic functions of ERG point to its involvement in: abrogating differentiation; facilitating cell invasion and epithelial to mesenchymal transition; and disrupting epigenetic, inflammatory, and DNA
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