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)

We have studied the effects of food restriction (FR) and substitution of fish oil (FO; omega 3) for corn oil (CO; omega 6) on breast tumor incidence and survival in mouse mammary tumor virus/v-Ha-ras transgenic (Onco) mice. The diets were as follows: group 1, 5% (wt/wt) CO fed ad libitum (AL); group 2, 5% CO, restricted calories (40% fewer calories than AL; FR); group 3, 20% CO fed AL; and group 4, 20% FO fed AL. After 3 years, 40% of FR Onco (group 2) mice were alive, whereas there were no survivors in the other three groups. Similarly, tumor incidence was reduced to 27% (5 out of 18) in FR animals (group 2), whereas it was 83% (11 out of 13) in group 1 mice, 89% (16 out of 18) in group 3 mice, and 71% (10 out of 14) in group 4 mice. These protective effects of FR on survival and tumor incidence were paralleled by higher expression of the tumor suppressor gene p53 (wild type) and free-radical scavenging enzymes (catalase and superoxide dismutase) in breast tumors. Immunoblotting showed less ras gene product, p21, and increased p53 levels in the tumors of FR mice. In addition, FR decreased RNA levels of c-erbB-2, interleukin 6, and the transgene v-Ha-ras in tumors. In contrast, analysis of hepatic mRNA from tumor-bearing FR mice revealed higher expression of catalase, glutathione peroxidase, and superoxide dismutase. Survival and tumor incidence were not influenced significantly by dietary supplementation with FO in place of CO. Taken together, our studies suggest that moderate restriction of energy intake significantly inhibited the development of mammary tumors and altered expression of cytokines, oncogenes, and free-radical scavenging enzymes.
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PMID:Dietary lipids and calorie restriction affect mammary tumor incidence and gene expression in mouse mammary tumor virus/v-Ha-ras transgenic mice. 760 20

Epithelial ovarian cancer probably occurs due to activation of several different combinations of genes, which produce cancers that vary biologically and clinically. We tested this hypothesis in 100 consecutive ovarian carcinomas by molecular biology techniques at the DNA and protein levels in three genes (erbB-2, myc, ras), which are frequently altered in this tumor system. Abnormally high expression of erbB-2 gene encoded p185 protein was observed in 31% of the samples, while erbB-2 gene amplification was detected by Southern analysis in 8%. ErbB-2 abnormal gene expression did not significantly affect the clinical outcome of patients, conferring a marginal worsening of survival. In 25 out of 96 (26%) tumor samples there was myc amplification. Higher levels of the ras-encoded p21 protein than in normal ovaries and benign ovarian tumors were found in 45% of the samples. Simultaneous overexpression of p185 and p21 was associated with shorter disease free (p = 0.02) and overall survival (p = 0.04) at significance levels notably higher than those observed for these oncoproteins singly. In addition, survival of patients with myc amplification and high p185/p21 coexpression was significantly worse (p < 0.05) than that of patients with normal levels. Our data suggest that concurrent abnormal gene expression may act synergistically to endow ovarian tumor cells with a highly aggressive phenotype. Evaluation of these genes may be helpful in the biological characterization of ovarian cancer and in defining individual patient prognosis.
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PMID:Concurrent abnormal expression of erbB-2, myc and ras genes is associated with poor outcome of ovarian cancer patients. 765 38

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

Expression of the ras and the c-erbB-2 oncogene products was investigated in 56 cases of human bladder transitional cell carcinoma and 6 samples of human normal bladder tissue using an immunohistochemical method. Thirty of the 56 cases of bladder tumor were found to be immunohistologically positive with the monoclonal anti-ras p21 antibody, while 19 of 56 cases were positive with the polyclonal anti-c-erbB-2 oncoprotein antibody. All 6 controls were negative with both antibodies. The ras p21 positive staining was found more frequently in the well or moderately differentiated, superficial and non-recurrent tumors than in the poorly differentiated (p < 0.01), muscle invasive (p < 0.05) and recurrent tumors (p < 0.01), while the c-erbB-2 gene product was more commonly detected in high-grade (p < 0.01), invasive (p < 0.01) and recurrent tumors (p < 0.05). Thus, the expression of either ras or c-erbB-2 was closely associated with the histological grade, clinical stage and recurrence of bladder transitional cell carcinomas.
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PMID:Correlation between the expression of oncogenes ras and c-erbB-2 and the biological behavior of bladder tumors. 809 2

A total of 44 cases of pancreatic lesions, including hyperplasia (six) cases, adenoma (mucinous cystadenomas [eight] and intraductal papillary adenoma [eight]), noninvasive intraductal papillary tumors (five), and invasive ductal carcinomas (17) were investigated possibly to establish a diagnostic marker. We examined the type of mucin secreted and immunoreactivities of antibodies to ras-p21 and c-erB-2 oncogene products. A significant decrease in the amount of mucin was found in invasive lesions, and this was associated with a shift toward production of neutral mucins and especially sialomucins. Hyperplasia and adenoma, in contrast, demonstrated a predominance of neutral mucin. The sulfated mucins found in normal epithelium were only very weakly stained in any of the tumor types. Thirty-three percent of non-invasive intraductal papillary tumors and 88% of invasive ductal adenocarcinomas demonstrated strong binding of the ras-p21 antibody. In contrast no obvious differences in expression of c-erbB-2 were evident between the groups. In conclusion, a combined mucin histochemical/immunohistochemical approach may facilitate accurate diagnosis.
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PMID:A mucous histochemical and immunohistochemical study of precancerous and neoplastic lesions in the human pancreas. 810 2

The role of oncogenes in carcinoma of unknown primary site (CUP) has not yet been elucidated. In the present study the expression of the c-myc p62, ras p21 and c-erB-2 p185 oncoproteins were studied by a 3-step immunoperoxidase technique in 26 cases of CUP. Positive immunoreactivity was observed in 96% of the cases for c-myc, 92% for ras and in 65% for c-erb-2, with at least half of tumor cells labelled in 85%, 92% and 58% respectively. The degree of staining intensity was considered moderate or strong in more than half of the cases for all oncogene products. In conclusion, our results showed that patients with CUP have an extremely high overexpression of all three oncogenes studied. Nevertheless, the biological role of these overexpressed oncoproteins, their relationship with different histological or clinical parameters and their diagnostic or prognostic value need further evaluation.
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PMID:Overexpression of C-myc, Ras and C-erbB-2 oncoproteins in carcinoma of unknown primary origin. 866 24

Previously we reported that neu differentiation factor (NDF)/heregulin (HRG) elevates tyrosine phosphorylation of its receptors erbB-3, erbB-4, and erbB-2 (through heterodimer formation). We also showed that both NDF/HRG and antibodies to erbB-2 can arrest growth and induce differentiation in breast cancer cells. In this study, we report on the mechanism of NDF/HRG-induced cellular effects. We show that NDF/HRG and antibodies to erbB-2 receptors up-regulate expression of p53 by stabilizing the protein. This is accompanied by up-regulation of the p53 inducible gene, p21CIP1/WAF1, in a variety of cell lines: MCF7 and their derivatives (MCF7/HER2, MN1 and MCF-7-puro), ZR75T and LnCap cells. The induction of p21 is further enhanced when cells are treated with both NDF/HRG and DNA-damaging chemotherapeutic agents (i.e. doxorubicin). The NDF/HRG mediated induction of p21 is dependent on wildtype p53, as it fails to occur in cells expressing dominant negative p53 (MDD2). Furthermore, p21 induction is capable of inactivating cdk2 complexes as measured by Histone H1 phosphorylation assays. Finally, we show that in primary cultures of breast and other cancers, p21 is significantly induced in response to NDF/HRG treatment. Collectively, these observations suggest that the mechanism of breast cancer cell growth inhibition and differentiation via erbB receptors activation is through a p53-mediated pathway.
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PMID:Neu differentiation factor (Heregulin) activates a p53-dependent pathway in cancer cells. 870 May 12

Ten cases of surgically resected small pancreatic tubular adenocarcinomas (PTA), grossly 2 cm or less were analyzed. Nine patients presented with symptoms. The cumulative 5 year survival rate was 14.8%. According to the criteria proposed by the Japanese Pancreatic Society, in three patients the PTA was stage I and in seven patients it was stage II. Immunohistochemical study detected overexpression of p53 in six PTA, of c-erbB-2 in four PTA, and of Ha-ras p21 in six PTA. the p53 overexpression was closely related to the poor clinical course (P < 0.05). All PTA focally had gastric mucin. In eight cases, mucous metaplasia was frequently found in the non-cancerous pancreatic tissues. Most of the mucous metaplastic cells had gastric mucin, and their staining patterns resembled those of the respective PTA. These findings support the putative hypothesis that most PTA arise from "gastric mucous cell metaplasia'. However, in two cases, mucous metaplasia was not found. In one other case, minute dysplastic glands determining the existence of in situ carcinoma or intrapancreatic metastasis were found in the islet of Langerhans, relatively distant from the main cancer. These findings also present the possibility that some PTA develop de novo without mucous metaplasia.
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PMID:Small pancreatic tubular adenocarcinomas: clinicopathological analysis with immunohistochemical and histochemical evaluation. 889 27

We have analyzed the bladder biopsies of six bladder cancer patients exposed to high levels of 2-naphthylamine and benzidine, 11 unexposed bladder cancer patients, six subjects with benign conditions of the bladder, and 16 healthy subjects. Immunohistochemical analysis of the p21 and p185 protein products, for overexpression of ras and c-erbB-2 oncogenes, was performed. Overexpression of ras was found in four of six exposed cancer patients, 3 of 11 unexposed cancer patients, zero of six benign disease patients, and zero of 16 healthy subjects. The odds ratio for ras overexpression, comparing exposed with unexposed cases, was 5.3 (90% confidence interval 0.6 to 64). Overexpression of c-erB-2 was apparently not associated with occupational exposure.
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PMID:Exposure to aromatic amines and ras and c-erbB-2 overexpression in bladder cancer. 892 23

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


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