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 alterations of multiple genes and their carcinogenic mechanism in cervical carcinoma were studies by molecular hybridisation, PCR and PCR-ASO techniques. The G-T point mutation in the 12th coden of Ha-ras was detected in cervical carcinomas with mutation frequency of 18.2% (8/44), and the amplification rate of Ha-ras gene was 45% (9/20). The c-erb B2 was amplified 3-30 fold with an amplification rate of 73.3% (11/15) in cervical carcinomas and 5 cancerous samples showed gene rearrangement. The elevated copies of c-myc gene with amplification rate of 91.7% (11/12) were observed in cervical carcinomas. The study of HPV16 viral gene showed that the existence of HPV16 DNA sequence was positively associated with c-myc gene amplification in cervical cancerous samples. The p53 and Rb tumor suppressor genes absence of deletion were observed in the 12 specimens of cervical carcinoma investigated. As mentioned above, the study on alteration and carcinogenic mechanism of multiple genes indicated that 3 oncogenes and HPV16 viral gene were activated or integrated throygh different mechanisms and they played roles in co-carcinogenesis. The integration of HPV16 gene might promote the c-myc gene at the early stage in carcinogenesis of cervical carcinoma, while the alteration of Ha-ras and c-erb B2 gene might be middle-late event. As for the roles of the p53 and Rb tumor suppresor gene in cervical carcinogenesis need further researches.
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PMID:[Carcinogenic mechanisms of multiple genes in cervical carcinoma]. 920 11

Overexpression of c-erbB-2/neu/HER-2 oncoprotein, a receptor tyrosine kinase, has been demonstrated in a variety of human cancers. To elucidate the involvement of c-erbB-2 in human skin carcinogenesis, we examined expression of the protein in skin samples from five cases of keratoacanthoma (KA), 10 of actinic keratosis (AK), 24 of squamous cell carcinoma (SCC) and 10 of basal cell carcinoma (BCC) and five samples of normal epidermis, using an immunohistochemical method on formalin-fixed, paraffin-embedded sections. Expression of c-erbB-2 was also examined in cultured SCC cell lines, a premalignant cell line and in cultured normal keratinocytes. Normal epidermal cells showed no or very little c-erbB-2 protein, but the covering epidermal layer of some tumours showed a few strongly positive cells. Samples of KA and AK showed barely detectable c-erbB-2 protein in only a few cases. Twenty of the 24 cases of SCC had elevated expression of c-erbB-2 protein, with a tendency to more positive cells in metastatic lesions. Five of the 10 cases of BCC stained for c-erbB-2 but more weakly than those of SCC. Reaction products of the positive cells were seen in the cytoplasm. All three cultured SCC cell lines stained for c-erbB-2 protein more strongly than the premalignant HaCaT or normal keratinocytes. Our results indicate the possible involvement of c-erbB-2 overexpression in the malignant conversion of keratinocytes.
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PMID:Increased level of c-erbB-2/neu/HER-2 protein in cutaneous squamous cell carcinoma. 921 24

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

Expression of intermediate filaments (IFs) has been suggested to be a reliable marker for differentiating epithelial and non-epithelial tumors. Moreover, the c-erbB-2 and p53 genes are considered to be involved relatively early in the process of human carcinogenesis. In order to elucidate the origin of uterine carcinosarcomas, we analyzed IF, c-erbB-2 and p53 expression in and the ultrastructural characteristics of clones derived from a human uterine-carcinosarcoma cell line, EMTOKA. The expression of IFs and other proteins in the EMTOKA clones was identical to that in the EMTOKA cell line. It and its 7 clones all expressed cytokeratins 8, 17, 18 and 19, vimentin, epithelial membrane antigen, S-100, myoglobin, type-II collagen, alpha-smooth-muscle actin, placental alkaline phosphatase and epidermal-growth-factor receptor. The c-erbB-2 and p53 expression levels of all the cell types of the EMTOKA cell line and its clones were the same. Interestingly, an ultrastructural study showed that the EMTOKA cell line and its clones at early and late passages possessed the characteristics of epithelial cell types without either transitional forms between the epithelial and stromal components or differentiation into sarcomatous components. The results of this study lend particular support to the combination tumor hypothesis that a precursor (stem) cell gives rise both to epithelial and to mesenchymal components during the histogenesis of uterine carcinosarcoma, the epithelial component of which appears to be dominant, suggesting that the established cell lines derived from a common stem cell.
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PMID:Uterine carcinosarcoma is derived from a single stem cell: an in vitro study. 931

To directly compare the expression patterns of different proteins known to be altered during mouse skin carcinogenesis, serial sections of normal and hyperplastic skin and tumors from various stages of 7,12-dimethylbenz[a]anthracene-initiated, 12-O-tetradecanoylphorbol-13-acetate-promoted female SENCAR mice were examined by immunohistochemistry. In untreated, normal mouse skin, keratin 1 (K1) and transforming growth factor-beta1 (TGFbeta1) were strongly expressed in the suprabasal layers, whereas integrin alpha6beta4 was expressed only in basal cells and only moderate staining for transforming growth factor-alpha (TGFalpha) was seen. In hyperplastic skin, TGFalpha expression became stronger, whereas expression of another epidermal growth factor (EGF) receptor ligand, heparin-binding EGF-like growth factor (HB-EGF), was strongly induced in all epidermal layers from no expression in normal skin. Likewise, the gap-junctional protein connexin 26 (Cx26) became highly expressed in the differentiated granular layers of hyperplastic skin relative to undetectable expression in normal skin. Expression of cyclin D1 in the proliferative cell compartment was seen in all benign and malignant tumors but not in hyperplastic skin. Beginning with very early papillomas (after 10 wk of promotion), expression of alpha6beta4 in suprabasal cells and small, focal staining for keratin 13 (K13) were seen in some tumors. Later (after 20-30 wk), focal areas of gamma-glutamyl transpeptidase (GGT) activity appeared in a few papillomas, whereas TGFbeta1 expression began to decrease. Cx26 and TGFalpha staining became patchier in some late-stage papillomas (30-40 wk), whereas suprabasal alpha6beta4, K13, and GGT expression progressively increased and K1 expression decreased. Finally, in squamous cell carcinomas (SCCs), there was an almost complete loss of K1 and a further decline in TGFalpha, HB-EGF, TGFbeta1, and Cx26 expression. On the other hand, almost all SCCs showed suprabasal staining for alpha6beta4 and widespread cyclin D1 and K13 expression, whereas only about half showed positive focal staining for GGT activity.
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PMID:Changes in protein expression during multistage mouse skin carcinogenesis. 932 43

Epidemiologic studies have shown that the risk of cancer in the ovarian surface epithelium is decreased by factors that suppress ovulation, whereas uninterrupted ovulation has been associated with increased risk. This suggests that ovulation may play a critical role in ovarian carcinogenesis. More recently, molecular studies have demonstrated alterations in specific oncogenes and tumor suppressor genes in ovarian cancers. Overexpression of the HER-2/neu oncogene occurs in approximately 30% of ovarian cancers and correlates with poor survival. Although mutation of the K-ras oncogene has been found in some mucinous ovarian cancers, mutations in this gene appear to be more common in borderline ovarian tumors. Amplification of c-myc occurs in approximately 30% of ovarian cancers and is more frequently seen in serous cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression of mutant p53 protein, occurs in 50% of stage III/IV and 15% of stage I/II ovarian cancers. Most p53 mutations in ovarian cancers are transitions, which suggests that they arise spontaneously rather than due to exogenous carcinogens. In contrast to the acquired genetic alterations described above that are a feature of sporadic ovarian cancers, 5-10% of ovarian cancers probably arise due to inherited genetic defects. Recently, the BRCA1 tumor suppressor gene has heen identified and shown to be responsible for most cases of hereditary ovarian cancer. Further studies are needed to augment our understanding of the molecular pathogenesis of ovarian cancer.
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PMID:Human ovarian cancer of the surface epithelium. 933 69

Our experiments were designed to identify initial biochemical and biological changes that occur during pancreatic carcinogenesis. TAKA-1, an immortal hamster pancreatic ductal cell line, was treated in vitro for up to 11 weeks with the pancreatic carcinogen N-nitorosobis(2-oxopropyl)amine (BOP). These treated cells were designated TAKA-1 + BOP. The growth of TAKA-1 and TAKA-1 + BOP cell lines was investigated in soft agar and in hamsters intradermally. The resulting tumor from TAKA-1 + BOP was re-cultured in vitro and designated TAKA-1 + BOP-T. Mutation of c-K-ras and p53 oncogenes, chromosomal changes, expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptor and several biochemical markers were examined in all cell lines. TAKA-1 + BOP but not TAKA-1 cells grew in soft agar and produced an invasive tumor in vivo. However, there were no differences in cell growth rate, DNA flow cytometry, or immunohistochemical findings between the non-transformed and transformed cells. TAKA-1, TAKA-1 + BOP and TAKA-1 + BOP-T cells all expressed mRNA of TGF-alpha and EGF receptor in a comparable pattern. DNA sequence analysis following polymerase chain reaction showed that neither TAKA-1 nor TAKA-1 + BOP cells has a mutation of c-K-ras or p53. Karyotype analysis demonstrated that TAKA-1 + BOP cells had more chromosomal abnormalities compared with TAKA-1 cells. Mutation of c-K-ras and p53 was not essential for carcinogenesis in hamster pancreatic ductal cells in vitro. In conclusion, immortality of the TAKA-1 cells caused expression of TGF-alpha to the same extent as in malignant cells. Chromosomal and ultrastructural patterns were the only differences detected between the non-transformed and BOP-transformed cells.
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PMID:In vitro pancreatic ductal cell carcinogenesis. 937 45

Expression of c-erbB-2 oncogene and mutant p53 protein were detected immunohistochemically in 14 cases of myoepithelioma and 6 cases of myoepithelial carcinoma of the salivary gland. Five of the 6 myoepithelial carcinomas and nine of the 14 myoepitheliomas were overexpression of c-erbB-2 oncoprotein. The salivary ductal epithelial cells near tumors were overexpression of c-erbB-2 oncoprotein. These results indicate that c-erbB-2 may be an initial oncogene during the histogenesis of myoepithelial tumors. The p53 protein was positive in five cases of the 6 myoepithelial carcinoma, whereas all myoepitheliomas were negative. The results indicate that the mutant p53 gene may play an important role in the carcinogenesis of myoepithelial carcinoma.
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PMID:[Expression of c-erbB-2 oncogene and mutation of p53 gene in myoepithelioma and myoepithelial carcinoma]. 938 34

An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.
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PMID:No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation. 946 Oct 34

The majority of human lung cancers originate from the carcinogenesis of bronchial epithelial cells. To study the malignant progression of human bronchial epithelial cells, we established a SV40T-transformed human bronchial epithelial cell line, and observed some biological and genetic changes of the cell line at different passages. In a 2-year culture, this cell line was approaching malignancy without obvious senescence. Cells in a later passage proliferated faster and required less growth factors than those of an early passage. After continued passaging, these cells were resistant to the terminal squamous differentiation effects of serum, and many of the cells grew anchorage independently. However, no tumor formed after cells were injected into nude mice. Some genetic alterations were found accompanying those morphological changes, such as 3p- and activation of c-myc, c-erbB-2 and bcl2, suggesting that those genetic alterations may contribute to the carcinogenesis of human bronchial epithelial cells at an early stage. This cell line should be particularly useful for studying the progression of human lung cancers.
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PMID:Establishment and characterization of a SV40T-transformed human bronchial epithelial cell line. 949 36


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