Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoter region of the epidermal growth factor (EGF) receptor has been identified by in vitro transcription using EGF receptor genomic DNA fragments as template and by primer extension and nuclease S1 mapping using EGF receptor mRNA. Six transcriptional start sites were identified. DNA sequence analysis shows that the promoter region contains neither a "TATA box" nor a "CAAT box," has an extremely high G+C content (88%), and contains five CCGCCC repeats and four (TCC)TCCTCCTCC repeats. This promoter region is situated close to or within a DNase I-hypersensitive site in A431 human epidermoid carcinoma cells, which overproduce the EGF receptor. The EGF receptor gene promoter has some resemblance to the promoter of the hydroxymethylglutaryl-CoA reductase gene and the early promoter of simian virus 40. This similarity may offer a clue to the mechanism by which the receptor gene is regulated.
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PMID:Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene. 299 99

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors prevent the conversion of HMG-CoA to mevalonate and thereby inhibit the synthesis of other products derived from this metabolite. This includes a number of small prenylated GTPases involved in cell growth, motility, and invasion. We studied the effect of HMG-CoA reductase inhibitors (fluvastatin and lovastatin) on in vitro invasion of human pancreatic cancer PANC-1 cells. Epidermal growth factor (EGF) induced a dose-dependent increase of PANC-1 cell invasion in a modified Boyden chamber assay. Stimulation of cancer cells with EGF induced translocation of RhoA from the cytosol to the membrane fraction and actin stress fiber assembly. Furthermore, Clostridium botulinum C3 transferase, a specific inhibitor of Rho, inhibited the ability of EGF to promote invasion, indicating that EGF-induced cancer cell invasion is regulated by Rho signaling. Treatment of PANC-1 cells with fluvastatin markedly attenuated EGF-induced translocation of RhoA from the cytosol to the membrane fraction and actin stress fiber assembly, whereas it did not inhibit the tyrosine phosphorylation of EGF receptor and c-erbB-2. The induction of cancer cell invasion by EGF was inhibited by the addition of fluvastatin or lovastatin in a dose-dependent manner. The effects of fluvastatin or lovastatin on cell morphology and invasion were reversed by the addition of all-trans-geranylgeraniol but not by the addition of all-trans-farnesol. These results suggest that HMG-CoA reductase inhibitors affect RhoA activation by preventing geranylgeranylation, which results in inhibition of EGF-induced invasiveness of human pancreatic cancer cells.
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PMID:Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. 1140 67