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 isoflavonoid kievitone potently inhibited the proliferation of the oestrogen receptor (ER)-positive breast cancer cell lines MCF-7 and T47D and the ER-negative breast cancer cell line SKBR3 (IC50 values 5-18 microM). DNA synthesis of MCF-7 cells stimulated by insulin-like growth factor 1, insulin-like growth factor 2, basic fibroblast growth factor or transforming growth factor alpha was inhibited by similar concentrations of kievitone (IC50 values 1-3 microM). DNA synthesis stimulated by 17, beta-oestradiol was also inhibited (IC50 = 6 microM). Compared with kievitone, genistein was 3-9 fold weaker as an inhibitor of the proliferation of the breast cancer cell lines and of growth factor-stimulated DNA synthesis. However, genistein was about 5-fold more potent than kievitone as an inhibitor of solubilised epidermal growth factor (EGF) receptor kinase activity and EGF receptor autophosphorylation.
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PMID:Potent inhibition of breast cancer cell lines by the isoflavonoid kievitone: comparison with genistein. 779 75

Human sarcomas arise suddenly, thus preempting the study of preneoplastic and early neoplastic lesions. To explore the natural history of these tumors we studied male mice carrying a heterozygous deletion of p53 and an activated HER-2/neu transgene (BALB-p53Neu mice), that develop urethral rhabdomyosarcomas with nearly full penetrance and early onset (4 months of age). Among genes prominently upregulated in preneoplastic tissue, and more highly expressed in tumors, we found the insulin-like growth factor 2 (Igf2) and tumor suppressors, p19Arf and p21Cip1. In urethral tissues of male mice p53 was less expressed than in female mice, whereas HER-2/neu was more expressed, a combination not found in other skeletal muscles of the same mice that could contribute to the anatomic and sexual specificity of BALB-p53Neu rhabdomyosarcoma. Upregulation of p19Arf and p21Cip1 was additively determined by HER-2/neu activation and by p53 inactivation. Silencing of p19Arf or p21Cip1 in rhabdomyosarcoma cell lines can inhibit cell growth and motility, thus suggesting that these genes can contribute to growth autonomy and malignancy of tumor cells. In vivo injection of gene-silenced cells highlighted selective variations in organ-specific metastatic ability, indicating that overexpression of p19Arf and p21Cip1 controlled both tumor cell-intrinsic properties and microenvironmental interactions. The onset of pelvic rhabdomyosarcoma in BALB-p53Neu male mice is triggered by the coincidental overexpression of HER-2/neu and hypoexpression of the residual p53 allele, that foster p53 loss, Igf2 autocriny and overexpression of p19Arf and p21Cip1, a phenotype that could provide novel potential targets for cancer prevention and therapy.
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PMID:Tumor suppressor genes promote rhabdomyosarcoma progression in p53 heterozygous, HER-2/neu transgenic mice. 2433 79