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)

Two genomic DNA clones encoding part of the mouse epidermal growth factor (EGF) receptor were isolated: an 8.0 kb insert that hybridized with the human EGF receptor kinase domain; and a 2.4 kb insert that mapped between the kinase and 3' autophosphorylation domains of the human EGF receptor gene. The 2.4 kb insert was further digested to a 2.0 kb fragment and a 0.4 kb fragment containing 49 residues that were almost identical to the corresponding human EGF receptor sequence. Ribonuclease protection studies with mouse RNA identified three exons of 170 kb, 105 kb, and 50 kb in the 2.0 kb probe that were less homologous to the corresponding human or rat mRNAs. Northern blot hybridizations identified two EGF receptor transcripts of 10 kb and 6 kb in normal, but not EGF-nonresponsive, mouse cell lines, and a single 9.5 kb transcript in rat cells. An additional 6.5 kb transcript from rat NRK cells was identified that is related to but not transcribed from the EGF receptor gene.
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PMID:Characterization of rodent epidermal growth factor receptor transcripts using a mouse genomic probe. 243 80

Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens for some human breast cancer cell lines, and expression of IGF-II mRNA in the oestrogen receptor-positive (ER+) and oestradiol (E2) stimulated human breast cancer cell line T47D is increased by E2, suggesting a role for IGF-II in the mitogenic response to E2. Very little information is available from the literature on the relation between growth inhibition by endocrine therapy and cellular production of IGF-II. Here we report on the effect of E2 and tamoxifen (TAM) on IGF-II mRNA and protein expression in the ER+T61 human breast cancer xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay. Untreated T61 tumours have a high baseline expression of IGF-II mRNA. TAM treatment of T61 tumours, which results in inhibition of tumour growth without tumour regression, reduced IGF-II mRNA expression approximately 10-fold after 48 h of treatment. E2 treatment of T61 tumours, which results in tumour regression, was accompanied by a more pronounced decrease in IGF-II mRNA expression in the tumour cells; 96 h after initiation of E2 treatment, there was almost no detectable IGF-II mRNA. Analyses of IGF-II protein showed that both treatments significantly reduced the concentration of IGF-II protein in the tumours. This down-regulation was found to be specific for IGF-II, since analyses of the effect of E2 on the expression of IGF-I mRNA, 36B4 mRNA, transforming growth factor alpha(TGF-alpha) mRNA, and epidermal growth factor (EGF) receptor mRNA in T61 tumours did not reveal any down-regulation. To further study the relation between inhibition of tumour growth and down-regulation of IGF-II, we exposed T61 tumours to a monoclonal antibody, alpha-IR3, which abolishes the physiological effect of IGF-I and IGF-II by blocking the binding of both growth factors to the type I IGF receptor. Treatment with alpha-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II). 843 11