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)

Differential expression of two enzymes, dipeptidyl peptidase IV (CD26/DPP IV) and thyroid peroxidase (TPO), in neoplastic thyroid tissues was studied by Northern blot analysis and histochemical analysis using 31 thyroid tissue specimens of various thyroid diseases. On Northern blot analysis, all 16 differentiated carcinomas (12 papillary and 4 follicular carcinomas) overexpressed CD26/DPP IV mRNA, whereas all 14 benign tissue specimens (4 normal thyroid, 4 Graves' disease, 2 adenomatous goiters and 4 follicular adenomas) showed faint expression of CD26/DPP IV mRNA. All 14 benign tissues expressed high levels of TPO mRNA, whereas all 12 papillary carcinomas strongly underexpressed TPO mRNA. A medullary carcinoma did not show any mRNA expression of either enzyme. TPO mRNA expression in differentiated carcinomas did not always correlate with mRNA expression of thyroglobulin, thyroid stimulating hormone receptor, and thyroid transcription factor-1. Northern blot analysis also revealed that CD26/DPP IV is a more specific marker of differentiated carcinoma than three proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2, and EGF-R. Histochemically, all 14 benign tissues were CD26/DPP IV negative and strongly TPO positive, while all 12 papillary carcinomas were strongly CD26/DPP IV positive and TPO negative. Three of 4 follicular carcinomas were histochemically positive for the two enzymes. These findings suggest that the differential expression of these two enzymes can be applied to study the thyroid tumorigenesis.
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PMID:[CD26/dipeptidyl peptidase IV and thyroid peroxidase as molecular markers for differentiated thyroid carcinoma]. 869 39

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

Inactivation of the "deleted in colon cancer" (DCC) gene on chromosome 18 is known to be associated with the tumorigenesis and metastasis of colorectal cancer. In the present study, we investigated the expression of DCC and the c-erbB-2 product in surgical specimens from 45 patients with breast cancer by immunohistochemical staining, and found the expression of DCC to be decreased in 23 (51%) tumors. In 8 years of follow-up, 11 of 22 (50%) patients with DCC-positive staining tumors, and 17 of 23 (74%) patients with DCC-negative tumors developed recurrence. The stratified analysis, according to the status of axillary lymph node metastasis, showed the same tendency. Overexpression of erbB-2 was detected in 13 (29%) of the 45 breast cancer specimens, but there were no differences in the relapse rate between patients with erbB-2 positive and those with erbB-2 negative tumors. Although the individual alteration of DCC or erbB-2 did not possess independent prognostic significance for the prediction of recurrence, patients with tumors having the double alteration of DCC-negative and erbB-2-positive showed adverse relapse-free survival (0.025 < P < 0.05). These findings suggest that a decrease in DCC expression and erbB-2 overexpression may influence the progression of breast carcinoma.
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PMID:Decreased expression of the DCC gene in human breast carcinoma. 893 Dec 21

The PEA3 group of transcription factors belongs to the ets family and is composed of 3 known members, PEA3, ERM and ER81, which are more than 95% identical within the DNA-binding ETS domain and exhibit 50% aa identity overall. Recently, transgenic mice bearing the c-erbB-2/neu oncogene have been shown to over-express PEA3 mRNA in mammary adenocarcinomas, suggesting a role for this gene family in mammary tumorigenesis. In the present work we characterized the mRNA expression levels of PEA3-group genes in a series of human epithelial breast cell lines. Each of the 3 genes was highly expressed in normal human HMEC 1001-7 and HMEC 219-4 cells. In breast-cancer cell lines, the 3 genes were highly expressed in the ER- MDA-MB-436, MDA-MB-330, MDA-MB-231 and BT-20 cell lines, but not in the ER+ MDA-MB-134-VI and ZR-75-1 cells. In an attempt to characterize the PEA3-group proteins in breast-cancer cells, we first produced and characterized specific antibodies against each of these 3 proteins. The anti-ERM and anti-ER81 antibodies recognized specific strong bands at approximately 72 kDa and 62 kDa, corresponding to ERM and ER81, respectively, in MDA-MB-231 and Hs-578T cells expressing significant levels of the 3 mRNAs. No protein was detected in MCF-7 cells expressing low levels of mRNA for PEA3-group-family genes, or in ZR-75-1 cells, where mRNA was undetectable by Northern blot. Although in vitro-translated PEA3 is specifically immunoprecipitated by anti-PEA3 anti-serum, we were unable to immunoprecipitate PEA3 protein from MDA-MB-231 and Hs-578T cells. In order to study the transcription factor activity of ERM, PEA3 and ER81 proteins in mammary-cancer cells, we tested their ability to transactivate a reporter plasmid containing 3 Ets-binding sites, and were able to show that, in all the breast-cancer cells tested, transfected ERM, PEA3 and ER81 are able to transactivate. Although the target genes of the PEA3 group of transcription factors in breast-cancer cells have yet to be determined, these genes have a potential role in the regulation of growth and the progression of human breast cancer.
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PMID:Expression of the PEA3 group of ETS-related transcription factors in human breast-cancer cells. 905 61

HER-2/neu expression in pancreatic adenocarcinoma has been inconsistently reported and has not been fully evaluated with respect to histologic grade and tumor grade heterogeneity. We studied HER-2/neu expression in a series of 79 primary pancreatic carcinomas using immunohistochemical methods, with expression scored for each histologic grade represented in each tumor. We found significantly lower expression of HER-2/neu in poorly differentiated (PD) portions of tumors-those areas lacking glandular differentiation-compared to well-differentiated (WD) and moderately differentiated (MD) portions of tumors. Forty-two of 68 (62%) invasive tumors with WD or MD glands showed moderate or strong expression of HER-2/neu in WD/MD areas; only 6 of 32 (19%) invasive tumors with PD areas showed similar expression in PD. In mutually exclusive patient sets, we also found a statistically different prevalence of HER-2/neu expression in patients with PD (6/32 cases; 19%) and without PD (29/47 cases; 62%) tumors (p < 0.001). Twenty-three cases had directly comparable areas of PD versus MD or WD. In 19 of 23 cases HER-2/neu expression was graded comparatively lower (or negative) in areas of PD than in MD or WD. Overall 46 of 79 cases (58%) showed moderate to strong HER-2/neu expression inclusive of all histologic grades, and 63 of 79 (80%) cases were HER-2/neu positive, if including weak or focal staining. There was no significant difference in the survival of patients with HER-2/neu-positive versus-negative tumors or in patients with versus without PD tumors. We have confirmed that although HER-2/neu gene expression is common to many pancreatic carcinomas, it is not common to tumors lacking glandular differentiation. HER-2/neu gene expression could not be related to survival differences--perhaps due to overall poor survival within adenocarcinomas of the pancreas--but the pattern of HER-2/neu expression suggests a relationship to glandular differentiation and early oncogenesis.
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PMID:HER-2/neu expression in pancreatic adenocarcinoma: relation to tumor differentiation and survival. 909 52

BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison group of stage II breast cancers were studied with regard to histopathological features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often DNA non-diploid, as well as being characterised by higher S-phase fraction values. These results suggest that BRCA1-induced breast cancers may manifest distinct tumour biological features of clinical importance.
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PMID:Tumour biological features of BRCA1-induced breast and ovarian cancer. 915 18

The class I tyrosine kinase growth-factor receptors include epidermal growth factor receptor (EGFR), ErbB2 (c-erbB-2, HER-2/neu), ErbB3 and ErbB4. To elucidate their role in the regulation of homeostasis and carcinogenesis, we examined the expression of the receptors in normal urothelium and in urothelial carcinoma by immunohistochemistry. EGFR was expressed in the basal cells of normal urothelium, while ErbB2, ErbB3 and ErbB4 were present mainly in the superficial layer. A distinct reciprocal distribution was observed between the EGFR and the remaining members of the subclass (P = 0.0001). Both BCL-2 protein and Ki-67 antigen (MIB-1) showed a strong positive association with EGFR (P = 0.002) and an inverse correlation with ErbB2, ErbB3 or ErbB4 (P = 0.0004, 0.0000, and 0.001, respectively). With regard to carcinoma, there was no important relationship between receptor overexpression and tumour grading (P > 0.1), while only EGFR overexpression was correlated with muscular invasion (P = 0.02). Coexpression of EGFR-ErbB3 and ErbB3-ErbB4 was more often detected in high-grade tumours and correlated with the extent of tumour invasion. Our data indicate that class I receptors are differentially expressed in normal urothelium in vivo, but an orchestrated expression pattern does not exist during tumorigenesis.
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PMID:Expression patterns of erbB receptor family in normal urothelium and transitional cell carcinoma. An immunohistochemical study. 923 Sep 11

Tumorigenesis is the result of sequential or multiple genetic alterations. The overexpression or amplification of various oncogenes in diverse human brain tumors have been observed. While numerous studies on the immunohistochemical demonstration of EGFR-overexpression have been reported, little has been found in the literature about the c-erbB-2 protein in human astrocytic tumors. In the present study, we evaluated the expression of EGFR and c-erbB-2 protein in 33 astrocytic tumors with immunohistochemistry. According to the World Health Organization brain tumor classification, the study included 9 low-grade astrocytomas (grade 2), 15 anaplastic astrocytomas (grade 3), and 9 glioblastomas multiforme (grade 4). The positive EGFR immunoreactivity was detected in 28 (85%) of 33 tumors. The expression of EGFR increased with the grade of malignancy in low-grade astrocytomas (67%), anaplastic astrocytomas (87%), and glioblastomas (100%). For the expression of c-erbB-2 protein, 17 (51.5%) of 33 tumors were positive immunostain, including 3 low-grade astrocytomas (37.5%), 9 anaplastic astrocytomas (81.8%), and 5 glioblastomas (62.5%). Different degrees of immunoreactivity for c-erbB-2 protein were found in variant grades of astrocytomas. However, the positive immunostain of EGFR displayed moderate or strong reactivity. The coexpression of EGFR and c-erbB-2 protein was found in 17 (15.5%) of 33 tumors. The results emphasize that the overexpression of EGFR parallels astrocytoma progession and higher frequency of c-erbB-2 immunoreactivity was seen in snaplastic astrocytomas and glioblastomas than in low-grade astrocytomas.
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PMID:Expression of epidermal growth factor receptors and c-erbB-2 proteins in human astrocytic tumors. 926 Apr 61

In order to study the interrelation between bcl-2, P53 and c-erbB-2 protein, their expression in 145 breast carcinomas were observed by immunohistochemical LSAB method. 19 cases were negative, 12 were positive for the three oncoproteins. 19 cases were positive for c-erbB-2 only. 20 positive for P53 only and 20 positive for bcl-2 only. 26 cases were positive for both P53 and c-erbB-2, 17 for both c-erbB-2 and bcl-2, 12 for both P53 and bcl-2. Strong inverse correlation was found between the expression of P53 and bcl-2 (P < 0.001). The P53 expression or the expression of both P53 and c-erbB-2 correlated with low histological grade, while the bcl-2 expression correlated with high histological grade (P < 0.05). The necrosis in tumors with only bcl-2 expression was less than those with c-erbB-2 or both c-erbB-2 and P53 expression (P < 0.02). Mitosis count was lower in tumors with only bcl-2 expression than those with expression of both c-erbB-2 and P53 (P < 0.05). The expression of c-erbB-2 and P53 proteins are associated with poor prognosis (P < 0.02, P < 0.05) but not affected by bcl-2. The results suggest that bcl-2, P53 and c-erbB-2 are involved in tumorigenesis and development of breast carcinoma with different biological effects.
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PMID:[The expression of bcl-2, P53 and c-erbB-2 onco-proteins in breast cancer and their clinicopathological significance]. 927 73

Recently reported morphologic and molecular genetic evidence suggests that some ovarian carcinomas arise from their benign and low malignant potential (LMP) counterparts. In order to help reach a better understanding of ovarian tumorigenesis, we studied a wide range of gene products involved in cellular growth regulation in archival material obtained from three groups of tumors with graduated malignant potential. Immunohistochemical staining was performed for Ki-67, proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), HER-2/neu-encoded receptor protein, p53 gene product, and multidrug resistance gene product (P-glycoprotein). The expression of EGFR, HER-2/neu-encoded receptor protein, and mutant p53 product was significantly lower in LMP tumors than in carcinomas (p < 0.05). HER-2/neu immunopositivity was more prevalent in adenocarcinomas than in LMP tumors, and the proportion of HER-2/neu-positive adenocarcinomas increased with the progression of the disease. The staining differences between LMP tumors and adenocarcinomas with antibodies against Ki-67, PCNA, and P-glycoprotein were not statistically significant. Immunohistochemical detection of EGFR, HER-2/neu, and p53 in ovarian epithelial tumor is relevant to ovarian tumorigenesis. It could serve as a powerful tool for the pursuit of retrospective studies focused on these important biologic markers.
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PMID:Immunohistochemical assessment of proliferation markers and altered gene expression in archival specimens of ovarian epithelial tumors. 939 93


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