Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used rat prostate cancer cell stable transfectants that lacked either endogenous fibroblast growth factor (FGF)-1 secondary to constitutive expression of FGF-1 antisense RNA (aFa2-transfectants) or endogenous FGF-2 isoforms secondary to constitutive expression of FGF-2 antisense RNA (bFa9-transfectants) to examine the potential synergistic effects of mitogen and androgen as modulators of proliferation. During culture on 5% charcoal-stripped fetal bovine serum (CS-FBS), FGF-1 caused a 2- to 2.5-fold increase in the proliferation of aFa2-transfectants that lacked endogenous FGF-1 and retained full expression of FGF-2 isoforms. In marked constrast, bFa9-transfectants that lacked FGF-2 isoforms and retained full expression of FGF-1 died with exponential kinetics when cultured on either 5% CS-FBS or 5% FBS in the absence of FGF-2. However, FGF-2 promoted bFa9-transfectant survival and exponential proliferation during culture on either 5% CS-FBS or 5% FBS. The nonmetabolizable androgen R1881 did not affect proliferation of either the aFa2- transfectants, the bFa9-transfectants, or the parental prostate cancer cells used to generate these transfectants. Additionally, neither of the androgen receptor antagonists RU23908 or bicalutamide affected either FGF-1-mediated aFa2-transfectant proliferation or FGF-2-mediated bFa9-transfectant proliferation during culture on 5% CS-FBS. Notably, transient transfection analyses established R1881 concentration-dependent induction of chloramphenicol acetyltransferase activity in both aFa2-transfectants and bFa9-transfectants. Thus, the failure of either androgen or antiandrogen to affect either FGF-mediated or FGF-independent antisense-transfectant proliferation is not attributable to absence of functional androgen receptors. The results indicate that FGF effects in these androgen-resistant antisense transfectants do not involve either androgen-dependent or androgen-independent, mitogen-mediated androgen receptor activation. Our studies show that these rat prostate cancer cells are characterized by both retention of functional androgen receptors during development of androgen resistance and mitogen-mediated, autocrine or paracrine (or both) modulated proliferation. These are two prominent properties characteristic of advanced human prostate cancer.
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PMID:Neither fibroblast growth factor-1 nor fibroblast growth factor-2 is an androgen receptor coactivator in androgen-resistant prostate cancer. 1169 May 59

As a transcriptional regulator, the androgen receptor (AR) regulates the expression of many genes that are essential for male sexual differentiation, including the development of both normal prostate and prostate cancer. The AR acts by binding to regulatory DNA sequences found on the promoters of regulated genes. The study of AR activity on such responsive promoters is greatly facilitated by the use of the reporter gene assay, which provides a quantitative and reproducible method for studying the activity of such promoters. Among the several reporter genes that can be used, the genes encoding luciferase (Luc) and chloramphenicol acetyltransferase (CAT) have been used most widely and successfully by researchers interested in AR-regulated promoters. Such studies have led to the identification and characterization of DNA regulatory elements mediating AR activity on responsive promoters and to an improved understanding of how AR regulates the transcription process. Described in this chapter is a method by which to generate and utilize Luc and CAT reporter gene plasmids driven by the promoter of a novel androgen-regulated gene, ETV1.
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PMID:Use of reporter genes to study promoters of the androgen receptor. 1976 5


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