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 parotid tumors were evaluated for the activation of the phosphotyrosine signaling pathway by Western blot, enzyme activity assay, and reverse transcriptase-polymerase chain reaction. Warthin's tumor and mucoepidermoid carcinomas had the greatest level of tyrosine phosphorylated proteins identified in plasma membrane fractions. These tumors, along with pleomorphic adenocarcinoma, showed high levels of membrane expression of the tyrosine kinase receptor, c-erbB-2, and phosphatidylinositol-3-kinase. Expression of the epidermal growth factor receptor was confined to normal tissue. The level of mRNA for c-erb was elevated only in mucoepidermoid carcinomas. Messenger RNA levels for ras were unchanged from control levels in all tumors, while the level of src mRNA was higher in the tumor samples than the normal parotid tissue. The activities of several signal transduction kinases, including protein kinase A and C were elevated in tumor tissue (7.7- to 18.9- and 0.4- to 3.7-fold higher, respectively), relative to surrounding normal tissue. While the level of glandular amylase was reduced (22%-0% of normal levels) in the tumor tissue, epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha) content was dramatically higher in the neoplastic tissue (10- to 170-fold and 4.6- to 6.0-fold, respectively). These results suggest that with the presence of elevated levels of EGF, TGFalpha, and the oncoprotein receptor c-erbB-2 in the membrane of parotid tumors, cell proliferation and activation of the phosphotyrosine signal transduction pathway may involve autocrine stimulation through the expression of high levels of growth factor and receptor in the same tissue.
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PMID:Alterations in the level of phosphotyrosine signal transduction constituents in human parotid tumors. 863 6

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

Cellular oncogenes have been shown to play crucial roles in the cell death process induced by cytotoxic agents. In this study, we have demonstrated that v-H-ras transformed NIH 3T3 cells but not other transformants (v-raf, v-src, v-erbB-2, v-fes and v-mos) exhibited a survival advantage to treatment by a DNA-damaging agent, methylmethanesulfonate (MMS). Subsequently, the biochemical and morphologic criteria of MMS-treated cells were examined. It was found that MMS induced v-H-ras transformants to go through necrosis, but it induced other transformed cells to undergo apoptosis. The levels of glutathione (GSH) within each transformant as well as in NIH 3T3 cells, were determined. The results showed that GSH levels within ras transformants were 2- to 7-fold higher than the levels in other transformants and normal NIH 3T3 cells. By using the GSH synthesis inhibitor buthionine sulfoximine, GSH levels were artificially reduced. This depletion, however, made ras transformed cells more sensitive to MMS killing, but the mode of cell death was still necrosis. Western blot analysis demonstrated that the anti-apoptotic protein Bcl-2 was constitutively expressed in ras transformed cells but not in NIH 3T3 or other transformed cells. The level of Bcl-2 was correlated with the resistant phenotype of ras transformants during MMS treatment. These observations suggest that GSH and Bcl-2 levels may cooperatively confer the resistant phenotype of ras transformants in response to MMS. In addition, the mode of cell death may possibly be determined at least in part by Bcl-2 protein.
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PMID:Differential induction of apoptosis in oncogene-transformed NIH 3T3 cells by methylmethanesulfonate. 868 3

Malignant insulinoma is an rare form of cancer with poor prognosis and a reported 5-year survival of 35%. Relatively little is known about the etiology of this disease or of the oncogenes and tumor suppressor genes that participate in its genesis and progression. To address this issue, several protooncogenes, including K-ras, N-ras, erbB-2, erbB-3,c-myc, c-fos, c-jun were examined. Also analyzed was the expression of the growth factors TGF-alpha, EGF, and insulin as well as the EGF receptor (EGF-R), p53 and the putative anti-metastasis gene nm23-H1. These were examined in malignant insulinomas, benign insulinomas, pancreatic B cell hyperplasias and in normal endocrine pancreas. Normal endocrine pancreas showed moderate immunoreaction for c-myc and a strong reaction for insulin. All other parameters were negative. Benign pancreatic B cell hyperplasias were slightly or moderately positive for N-ras and TGF-alpha, and were weakly positive for EGF-R. They were strongly positive for c-myc and insulin. In malignant insulinomas there was strong immunoreaction for c-myc, TGF-alpha, N-ras, K-ras and p53. Insulin reaction was moderate or strong. Molecular genetic studies have been performed for the presence of activating point mutations in codon 12 of the c-K-ras oncogene. Mutations were detected using primer-mediated, mutant-enriched, polymerase chain reaction-restriction fragment length polymorphism analysis and were further characterized by allele-specific oligonucleotide hybridization. Four out of six patients with malignant insulinoma and two out of eight patients with benign insulinoma harbored K-ras point mutations at codon 12. All patients with mutated K-ras oncogene also had elevated levels of p53 protein as well as c-myc and TGF-alpha. In one extremely malignant case we found concomitant mutation at codon 12 of K-ras and codon 61 of the N-ras gene. Our data are consistent with the idea that malignant progression is accompanied by the progressive accumulation of multiple genetic lesions and suggest that activation of myc, TGF-alpha and ras genes may be early events in the development of insulinoma.
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PMID:Molecular genetics of malignant insulinoma. 871 89

Expression of P21, P53, P185 proteins, mutations of ras, p53 genes in colorectal adenoma, carcinoma and transitional mucosa were studied using immunohistochemicstry and PCR-RFLP methods. The results showed that the positive rates of P21, P53 and P185 proteins in colorectal adenoma were 53.3%, 27.6% and 13.3% respectively, the expression of P21 and P53 were associated with the malignant potential of adenoma. The positive rates of P21, P53 and P185 proteins in colorectal carcinoma were 72.9%, 37.8% and 47.2% respectively. 9 adenomas and 40 carcinomas contained more than two protein expressions and their co-expression was associated with the malignant potential of adenoma and the prognosis of carcinoma. The mutation rates of ras gene in colorectal adenoma and carcinoma were 26.7% and 41.9% respectively. The ras gene mutation was associated with the malignant potential of adenoma. The mutation rates of p53 gene (codon 248) in adenoma and carcinoma were 3.3% and 14.9% respectively. The prognosis of patients having gene mutation of both ras and p53 were poor. The results suggested that the alterations of ras, p53 and c-erbB-2 genes are involved in the tumorigenesis and development of colorectal carcinoma.
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PMID:[Detection of the expression of P21, P53, P185 proteins and the mutation of ras, p53 genes in colorectal adenoma and carcinoma]. 873 90

It has been reported that breast tumors that overexpress c-erbB-2/neu are less responsive to certain adjuvant chemotherapy regimens than those that express a normal amount of the gene product. To investigate whether overexpression of the c-erbB-2/neu-encoded p185 can indeed lead to increased chemoresistance in breast cancers, we introduced the human c-erbB-2/neu gene into the very low p185-expressing MDA-MB435 human breast cancer cells and examined Taxol sensitivities among the parental MDA-MB-435 cells and stable transfectants which express increased levels of p185. The p185-overexpressing MDA-MB-435 transfectants were more resistant to Taxol than the parental cells. The increased Taxol resistance was not accompanied by changes in doubling time and S-phase fraction. The increased Taxol resistance was independent from oncogenic transformation since it was observed only in c-erbB-2/neu-transformed cells and not ras-transformed cells when oncogene-transformed NIH3T3 cells were examined. To study whether p185 induced Taxol resistance through the mdr-1 pathway, we examined the mdr-l-encoded p170 levels in these transfectants. The MDA-MB-435 cells expressed very low levels of p170 and there was no increase of p170 expression in the p185-overexpressing MDA-MB-435 transfectants. Furthermore, these transfectants were not sensitized to Taxol treatment by mdr-1 blocker thioradazine. These data demonstrated that overexpression of c-erbB-2/neu can lead to intrinsic Taxol resistance independent from mdr-1 mechanisms.
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PMID:Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. 880 11

In an effort to understand the role of specific fats on carcinogenesis, we have studied the effects of lipids derived from cancer patients on components associated with the regulation of proliferation. The treatment of tumor cells with patient-derived fats produced increased cell proliferation, as indicated by shorter doubling times. The effects of patient-derived lipids on the expression of ras, c-jun, c-erbB-2, and p53 gene products were examined. The cellular expression of the ras proto-oncogene product was increased in both colon tumor cell lines, following lipid treatment. However, c-jun proto-oncogene expression was elevated in HT-29 cells and appeared unchanged in SK-Co-1 cells after lipid treatment. Treatment of HT-29 tumor cells with patient-derived fats produced an enhancement of the p53 gene product, whereas fat treatment reduced p53 expression in SK-Co-1 tumor cells. Further separation of the patient-derived fats indicated that the amplification of p53 gene expression in HT-29 cells could be achieved primarily by addition of the diacylglycerides fraction. Addition of the purified fatty acids, comprising the diglyceride fraction, indicated that the fatty acids, 16:1, 18:0, and 18:1, induced the most significant increases in p53 expression by HT-29 cells. These alterations caused by cancer patient-derived fats are consistent with the loss of normal growth regulation and may explain the epidemiologic association between certain fats and carcinogenesis.
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PMID:Modulation of colon tumor oncogene expression by cancer patient-derived lipids. 884 66

Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha-ras, infected with a recombinant retroviral vector containing the human c-erB-2 proto-oncogene (MCF10A-HE cells), show a higher invasive index than either the single transfectant (MCF10A-H) or MCF10A-erB-2(MCF10A-E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A-HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A-H, MCF10A-E, and the parental cells. Dot-blot analysis of gelatinase A and TIMP-2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP-2 expression in both single and double transformants. Furthermore, MCF10A-HE cells show more MMP-2 activity than parental MCF10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A-HE cells compared to parental cells, MCF10A-H and MCF10A-E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erB-2 and Ha-ras co-expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas.
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PMID:Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes. 884 40

Terminally differentiated cells are specialized cells unable to proliferate that constitute most of the mammalian body. Despite their abundance, little information exists on the characteristics of cell cycle control in these cells and the molecular mechanisms that prevent their proliferation. They are generally believed to be irreversibly restricted to the G0 state. In this report, we define some features of a paradigmatic terminally differentiated system, the skeletal muscle, by studying its responses to various mitogenic stimuli. We show that forced expression of a number of cell cycle-regulatory genes, including erbB-2, v-ras, v-myc, B-myb, ld-1, and E2F-1, alone or in combinations, cannot induce terminally differentiated skeletal muscle cells (myotubes) to synthesize DNA. However, serum-stimulated myotubes display a typical immediate-early response, including the up-regulation of c-fos, c-jun, c-myc, and ld-1. They also elevate the expression of cyclin D1 after 4 hours of serum treatment. All these events take place in myotubes in a way that is indistinguishable from that of quiescent, undifferentiated myoblasts reactivated by serum. Moreover, pretreatment with serum shortens the time required by E1A to induce DNA synthesis, confirming that myotubes can partially traverse G1. Serum growth factors do not activate late-G1 genes in myotubes, suggesting that the block that prevents terminally differentiated cells from proliferating acts in mid-G1. Our results show that terminally differentiated cells are not confined to G0 but can partially reenter G1 in response to growth factors; they contribute to a much-needed definition of terminal differentiation. The important differences in the control of the cell cycle between terminally differentiated and senescent cells are discussed.
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PMID:Terminally differentiated skeletal myotubes are not confined to G0 but can enter G1 upon growth factor stimulation. 885

A 58-year-old male presented multiple papules on the nose for over 10 years. Excisional biopsy revealed angiofibroma with perivascular fibrosis and coarse collagen fibers. Investigation for internal malignancies revealed gastric cancer. Messenger RNA for HER-2/neu and c-ras were found both in the lesions of the skin and stomach. We propose the term, fibropapule multiplex of the nose, which may be a variant of Cowden's disease associated with occult internal malignancy.
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PMID:Fibropapule multiplex of the nose: a variant of Cowden's disease? 886 82


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