Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In searching for androgen-responsive genes in human prostate cancer cells, we have isolated two cDNAs that encode alternate forms of a novel Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF). The SGEF mRNA is widely expressed in human tissues, and the predicted 871-amino acid SGEF protein contains Dbl homology and pleckstrin homology domains as well as an N-terminal proline-rich domain, a C-terminal Src homology 3 domain, and two nuclear localization signals. The second cDNA encodes a 139-amino acid N-terminally truncated form of SGEF designated C-terminal SGEF (CSGEF). In contrast to SGEF, CSGEF mRNA expression is restricted to prostate and liver. Moreover, CSGEF expression is up-regulated by androgens in LNCaP cells, whereas that of SGEF is not. Up-regulation of CSGEF was sensitive to actinomycin D but did not require new protein synthesis. The SGEF gene is located on chromosome 3q25.2 and consists of at least 15 exons. Based on the structure of the SGEF and CSGEF cDNAs, we deduced that CSGEF expression is controlled by an alternate androgen-responsive promoter of the SGEF gene. We hypothesize that SGEF is a ubiquitous regulator of Rho guanosine triphosphatases, whereas CSGEF may function as an androgen-induced regulator of Rho guanosine triphosphatase activity in epithelial cells of the human prostate.
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PMID:Isolation of the novel human guanine nucleotide exchange factor Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF) and of C-terminal SGEF, an N-terminally truncated form of SGEF, the expression of which is regulated by androgen in prostate cancer cells. 1269 79

The purpose of this study was to investigate the potential roles of the SH3-containing guanine nucleotide exchange factor (SGEF) in human prostate cancer. Experimental data showed that SGEF was overexpressed in human prostate cancer cells and specimens. The reduction of SGEF expression through an SGEF-targeting siRNA in androgen-independent C4-2 and C4-2B cells suppressed both anchorage-dependent and anchorage-independent growth. In addition, the androgen receptor (AR) antagonist bicalutamide further strengthened this inhibitory effect due to the suppression of the elevated AR transactivation after knockdown of SGEF. Collectively, our results provide the first demonstration that SGEF is a novel promoter of human prostate cancer progression and development.
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PMID:SGEF is overexpressed in prostate cancer and contributes to prostate cancer progression. 2282 26

Previously, we demonstrated an elevated SH3-containing guanine nucleotide exchange factor (SGEF) expression in clinical specimens with prostate cancer and implicated the role of SGEF in prostate tumorigenesis. However, the molecular mechanism behind the SGEF regulation of prostate cancer development is not known. In this study, we show that SGEF expression delays epidermal growth factor receptor (EGFR) degradation in prostate cancer cells and is independent from its guanine nucleotide exchange factor (GEF) function. We further show that the delayed degradation is due to a delay in EGFR trafficking from early to late endosomes and not to a decrease in EGFR ubiquitination. Finally, we show that depletion of SGEF significantly inhibits epidermal growth factor-induced EGFR signaling cascade and cell migration in the prostate cancer cells. We report for the first time an SGEF function for RhoG that excludes GEF and the ability of SGEF to enhance EGFR stability and signaling by delaying its lysosomal sorting and degradation. This could be one mechanism by which SGEF contributes to prostate cancer progression.
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PMID:SGEF enhances EGFR stability through delayed EGFR trafficking from early to late endosomes. 2366 35