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)

Human bladder carcinomas often express high levels of the epidermal growth factor (EGF) receptor. In three human bladder carcinoma cell lines (OBR, T24, and 647V), we show that two EGF receptor ligands, namely EGF and transforming growth factor alpha, enhanced the apoptosis due to serum starvation on cells cultured as monolayers. Conversely, EGF and transforming growth factor alpha prevented apoptosis when the same serum-starved cells were cultured as three-dimensional spheroids. Both stimulation and inhibition of apoptosis by EGF were associated with p21 WAF1/CIP1 overexpression. In 647V spheroids, EGF protection against radiation-induced apoptosis was negated by genistein and tyrphostin AG1478, suggesting that blockade of the EGF signal transduction in patients with bladder cancer may improve the radiotherapy efficacy.
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PMID:Two- and three-dimensional cell structures govern epidermal growth factor survival function in human bladder carcinoma cell lines. 926 96

Intestinal trefoil factor (ITF) is an essential regulator of colonic epithelial restitution, the rapid migration of colonocytes over mucosal wounds. High levels of ITF are frequently present in colorectal cancers and derived cell lines. Mucosal restitution requires the detachment of epithelium from substrate, which would be expected to induce apoptosis. However, mice deficient in ITF showed an increase in colonocyte apoptosis unaccompanied by changes in expression of receptor-related (TNFR/Fas) or stress-related (Bcl-family) cell death regulators. An ITF-expressing colonic (HT-ITF1) cell line was resistant to apoptosis induced by serum starvation and ceramide. Exogenous ITF also protected another human colonic carcinoma-derived cell line (HCT116) and a nontransformed rat intestinal epithelial cell line (IEC-6) from apoptosis. This effect was abrogated by wortmannin and tyrphostin A25, indicating the potential involvement of phosphatidylinositol 3-kinase and epidermal growth factor (EGF) receptor activation. Expression of phosphorylated Akt, which lies downstream of phosphatidylinositol 3-kinase activation, was elevated in this HT-29-ITF line. p53-dependent cell death in the AGS human gastric cancer cell line after etoposide was similarly inhibited by transient expression of ITF but not a C-terminal truncation mutant of ITF, and it required functional phosphatidylinositol 3-kinase and EGF receptor. These findings support a central role for ITF in the maintenance of intestinal mucosal continuity, and conversely demonstrate the potential for ITF expression to confer resistance of colorectal tumors to therapy.
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PMID:Intestinal trefoil factor confers colonic epithelial resistance to apoptosis. 1063 60

The ErbB receptor tyrosine kinase family consists of the epidermal growth factor (EGF) receptor (ErbB1) and three related receptors (ErbB2, ErbB3, ErbB4). Their intrinsic tyrosine kinases can be activated by receptor-dimerization induced by numerous ligands or overexpression. ErbB receptors are frequently overexpressed in breast cancer, and their overexpression is associated with protection from apoptosis. To directly assess their role in apoptosis sensitivity of breast cancer cells, we established MCF-7 breast carcinoma cell lines overexpressing each ErbB receptor alone or in all possible pairs. Overexpression of ErbB1, ErbB2 and ErbB4 receptors was enough to activate them as judged by their phosphorylation, whereas co-expression of other ErbB receptors was necessary for the phosphorylation of the ErbB3. Surprisingly, overexpression of the ErbB receptors even when combined with treatment with their ligands (EGF, transforming growth factor alpha, betacellulin, neuregulins) failed to protect the MCF-7 cells from cell death induced by either tumor necrosis factor (TNF) or serum starvation. During starvation TGF-alpha, however, increased the cell size of the ErbB1 overexpressing cell line, and neuregulin1-beta1 increased that of all cell lines. In conclusion, our data does not support the role of ErbB receptors in the regulation of cell death induced by TNF or serum starvation, and the observed association in breast cancer may be due to other concomitant changes.
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PMID:Cell death induced by TNF or serum starvation is independent of ErbB receptor signaling in MCF-7 breast carcinoma cells. 1079 81