Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. To identify new senescence regulatory genes that might play a role in tumorigenesis, we have designed and performed a large-scale antisense-based genetic screen in primary mouse embryo fibroblasts (MEFs). Out of this screen, we have identified five different genes through which loss of function partially bypasses senescence. These genes belong to very different biochemical families: csn2 (component of the Cop9 signalosome), aldose reductase (a metabolic enzyme) and brf1 (subunit of the RNA polymerase II complex), S-adenosyl homocysteine hydrolase and Bub1. Inactivation, at least partial, of these genes confers resistance to both p53- and p16INK4a-induced proliferation arrest. Furthermore, such inactivation inhibits p53 but not E2F1 transcriptional activity and impairs DNA-damage-induced transcription of p21. Since the aim of the screen was to identify new regulators of tumorigenesis, we have tested their inactivation in human tumors. We have found, either by northern blot or quantitative reverse transcriptase-PCR analysis, that the expression of three genes, Csn2, Aldose reductase and Brf1, is lost at different ratios in tumors of different origins. These genes are located at common positions of loss of heterogeneity (15q21.2, 7q35 and 14q32.33); therefore,we have measured genomic losses of these specific genes in different tumors. We have found that Csn2 and Brf1 also show genomic losses of one allele in different tumors. Our data suggest that the three genes identified in the genome-wide loss-of-function genetic screen are putative tumor suppressors located at 15q21.2; 7q35 and 14q32.33.
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PMID:Cellular senescence bypass screen identifies new putative tumor suppressor genes. 1796 25

Here, we aimed to investigate the expression of chromobox homolog 8 (CBX8) in nucleus pulposus (NP) cells from rat intervertebral disc (IVD) and its function in DNA damage and repair. NP cells were isolated from healthy rat IVD for immunohistochemistry staining. Small interfering RNA (siRNA) of CBX8 was applied for gene silencing, and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to determine mRNA levels of CBX8, type II collagen, and proteoglycans. Cell proliferation and cell cycle were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-forming assay, and flow cytometry. Hydrogen peroxide (H2O2) was added to simulate DNA oxidative damage, and expression of CBX8 was examined using RT-PCR and Western blot. After five passages, mRNA levels of type II collagen and proteoglycans decreased but that of CBX8 increased. When CBX8 was silenced by siRNA, the expressions of CBX8, type II collagen and proteoglycans declined, and the cell growth was inhibited. Besides, cell cycle was slowed down as most cells were arrest in G0/G1 phase. Furthermore, CBX8 expression went up responding to DNA oxidative damage caused by H2O2. The data indicated that CBX8 plays important roles in cell proliferation and DNA damage. Cell proliferation and cell cycle were stimulated by CBX8, which may be associated with INK4A-ARF pathway. Moreover, CBX8 plays a role in DNA damage which made it a potential gene therapy target for treatment of disc degeneration.
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PMID:Investigation of the relationship between chromobox homolog 8 and nucleus pulposus cells degeneration in rat intervertebral disc. 2357 36

Infection with high-risk human papillomavirus (HPV) type 16 is an independent risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC). However, it is unclear whether viral integration is an essential hallmark in the carcinogenic process of OSCC and whether HPV integration correlates with the level of viral gene transcription and influences the expression of disrupted host genes. We analyzed 75 patients with OSCC. HPV16-positivity was proven by p16(INK4A) immunohistochemistry, PCR and FISH. Viral integration was examined using DIPS- as well as APOT-PCR. Viral E2, E6 and E7 gene expression levels were quantified by quantitative reverse transcriptase (RT-q)PCR. Expression levels of 7 human genes disrupted by the virus were extracted from mRNA expression profiling data of 32 OSCCs. Viral copy numbers were assessed by qPCR in 73 tumors. We identified 37 HPV16-human fusion products indicating viral integration in 29 (39%) OSCC. In the remaining tumors (61%) only episome-derived PCR products were detected. When comparing OSCC with or without an integration-derived fusion product, we did not find significant differences in the mean RNA expression of viral genes E2, E6 and E7 or the viral copy numbers per cell, nor did the RNA expression of the HPV-disrupted genes differ from either group of OSCC. In conclusion, our data do not support the hypothesis that integration affects the levels of viral and/or HPV-disrupted human gene transcripts. Thus constitutive, rather than a high level, of expression of oncogene transcripts appears to be required in HPV-related OSCC.
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PMID:Comprehensive analysis of HPV16 integration in OSCC reveals no significant impact of physical status on viral oncogene and virally disrupted human gene expression. 2458 76


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