Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genomic alterations in primary breast cancer play a role in the initiation and progression of the disease. We have analyzed the molecular events involved in the initiation and progression of the neoplastic process in an in vitro experimental system. Immortalization of human breast epithelial cells (HBEC) is associated with 3:9 translocation, p53 mutation and microsatellite instability (MSI) of chromosomes 11p13, and 17p. BP1-E cells, derived from the immortalized MCF-10F cells transformed by the carcinogen benzo(a)pyrene (BP), express in vitro growth advantage, anchorage independence, enhanced chemoinvasiveness, loss of ductulogenic capabilities and tumorigenesis in a heterologous host. This neoplastic progression is also associated with mutations and/or amplification of c-H-ras, int-2, c-neu, c-myc and MDM2, MSI at 11q25 and 13q12-q13 and loss of heterozygosity at 17p. In order to test whether chromosomes 11 or 17 play a functional role in the phenotypic expression of transformation of BP1E cells, we utilized microcell-mediated chromosome transfer (MMCT) technique for inserting the corresponding normal chromosomes to these transformed cells. BP1E cells were transfected with PsV2neo plasmid and fused with microcells obtained from the mouse cell line A9, containing a normal chromosome 11 or 17 (A9-11neo and A9-17neo cells, selected in G418 and cloned. Sixteen primary microcell hybrids from each chromosome transfer, designated BP1E-11neo and BP1E-17neo survived selection in G-418 containing medium. A single clone from each group, BP1E-11neo #145 and BP1E-17neo D100, survived subcloning and were utilized for a detailed panel of analyses. The presence of a donor chromosome was confirmed by dual color fluorescence in situ hybridization (FISH), southern blot analysis of the marker vector pSV2neo, and microsatellite polymorphism analysis. The transfer of the normal chromosomes 11 and 17 resulted in a 50% and 90% inhibition of cell growth respectively, and reduced both colony efficiency and colony size. Telomerase activity was significantly reduced only by chromosome 17 insertion, providing a possible explanation for the more significant senescence observed in BP1E-17neo D100 cells. Microsatellite polymorphism analysis revealed that three loci, 11q13-23, 11q23.1, and 11q23.3 (markers D11S911, DRD2, and D11S29) were retained in BP1E-11neo #145 cells, and two, 17q24.2-25.2, 17q25.2 (markers D17S515 and D17S785 were retained in BP1E-17neo D100 cells. We conclude that the specific regions of normal chromosomes 11 and 17 transferred play a functional role in the expression of immortal and transformed phenotypes of HBEC in vitro.
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PMID:Functional roles of chromosomes 11 and 17 in the transformation of human breast epithelial cells in vitro. 1049 42

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a]P) and acts as a potent mutagen in mammalian systems. However, the molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. We have used malignant human bronchial epithelial cells (16HBE-T) transformed by exposure to anti-BPDE to help characterize these possible molecular mechanisms. We have previously observed overexpression of HER2/neu in 16HBE-T. To further investigate the effects of HER2/neu on 16HBE-T cell biologic phenotype, we inhibited HER2/neu expression using RNA interference. Silencing of HER2/neu in 16HBE-T cells was performed in vitro using retrovirus-delivered short hairpin RNA (shRNA). Silencing of HER2/neu in 16HBE-T cells resulted in significant increases and decreases in the proportions of cells in G0/G1 phase (67.1+/-2.1%) and in S phase (17.3+/-4.1%), respectively, and significantly reduced cell viability and colony formation rate. These results may help to explain epithelial cell transformation following exposure to anti-BPDE, and suggest an oncogenic role for HER2/neu in anti-BPDE-induced carcinogenesis.
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PMID:Effects of silencing of HER2/neu gene in anti-BPDE-transformed cells. 1899 21

Genetic alterations of the c-myc, c-neu and int-2 oncogenes have been reported in human breast cancer. In order to determine if these oncogenes are activated at different stages of breast cancer progression, we are using an in vitro system in which human breast epithelial cells (MCF-10F) have been transformed with benzo(a)pyrene(BP) or dimethylbenz(a)anthracene (DMBA). DMBA-treated cells gave rise to clones D3 and D3-1, BP-treated cells gave rise to clones BP1 and BP1-E. BP1-E cell line, derived from BP1 cell line, was tumorigenic in SCID mice. Southern blot analysis detected gene amplification and rearrangement of the int-2 oncogene in BP1 and BP1-E cells, but no changes were detected in D3 and D3-1 cells. Amplification of c-neu gene was only observed in BP1 and BP1-E cell lines. Neither amplification nor rearrangement was detected for the c-myc gene. At the transcriptional level, Northern blot analysis showed that int-2 mRNA was increased 1.5, 1.8, 1.3 and 2.0-fold in the BP1, BP1-E, D3 and D3-1 cell lines respectively. c-neu mRNA was increased 8.0-fold in BP1 and BP-1E cells and c-myc mRNA was increased 1.5-fold in D3 cells, but no changes were detected in the other cell lines. The data indicate that BP treatment induces changes both at the genomic and transcriptional level. However, none of the differences explain the tumorigenic properties of the BP1-E cell line. DMBA treatment induces changes that are only reflected at transcriptional level for the two oncogenes studied. Whereas none of these oncogenes can be considered the driving force in the expression of the tumorigenic phenotype, the interaction among them or with other oncogenes in the expression of the transformation phenotype cannot be ruled out.
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PMID:Activation of C-myc, C-Neu and int-2 oncogenes in the transformation of the human breast epithelial-cell line mcf-10f treated with chemical carcinogens in-vitro. 2155 25