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c-Myc mRNA (c-myc + mrna)
Selected AbstractsThe PVT-1 oncogene is a Myc protein target that is overexpressed in transformed cells,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2007Letizia Carramusa The human PVT-1 gene is located on chromosome 8 telomeric to the c-Myc gene and it is frequently involved in the translocations occurring in variant Burkitt's lymphomas and murine plasmacytomas. It has been proposed that PVT-1 regulates c-Myc gene transcription over a long distance. To get new insights into the functional relationships between the two genes, we have investigated PVT-1 and c-Myc expression in normal human tissues and in transformed cells. Our findings indicate that PVT-1 expression is restricted to a relative low number of normal tissues compared to the wide distribution of c-Myc mRNA, whereas the gene is highly expressed in many transformed cell types including neuroblastoma cells that do not express c-Myc. Reporter gene assays were used to dissect the PVT-1 promoter and to identify the region responsible for the elevated expression observed in transformed cells. This region contains two putative binding sites for Myc proteins. The results of transfection experiments in RAT1-MycER cells and chromatin immunoprecipitation (ChIP) assays in proliferating and differentiated neuroblastoma cells indicate that PVT-1 is a downstream target of Myc proteins. J. Cell. Physiol. 213: 511,518, 2007. © 2007 Wiley-Liss, Inc. [source] HER2 signaling enhances 5,UTR-mediated translation of c-Myc mRNAJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2004Enrico Galmozzi The increased levels of c-Myc protein observed previously in an ovarian carcinoma cell line stably transfected to express HER2 has suggested a role for the HER2 pathway in c-Myc expression. Analysis of HER2-transfected cells stimulated with heregulin ,1 (HRG) revealed increased c-Myc protein levels but not a corresponding increase in c-Myc mRNA expression or any change in c-Myc protein half-life. Transfection of HER2-overexpressing cells with a construct containing the 5, untranslated region (5,UTR) of c-Myc mRNA originated from the P2 promoter and placed upstream of the Renilla luciferase gene, enhanced reporter expression upon stimulation with HRG. The HRG-mediated increase in reporter activity correlated with the HRG-mediated induction observed for c-Myc protein, identifying the P2-derived leader (P2L) of c-Myc mRNA as the cis -element involved in c-Myc translational induction. Both the increase in c-Myc protein levels and P2L-enhanced translational activity were inhibited by the PI3K inhibitor wortmannin. Together, these results demonstrate that HRG stimulation of HER2 overexpressing cells leads to enhanced c-Myc protein synthesis through activation of the PI3K/Akt/mTOR pathway and that the P2L of c-Myc mRNA is the element responsible for induction of c-Myc translation. © 2004 Wiley-Liss, Inc. [source] Mesalazine downregulates c-Myc in human colon cancer cells.ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2007A key to its chemopreventive action? Summary Background, Dysplasia and malignant transformation of colonocytes in ulcerative colitis are associated with overexpression of c-Myc and genes regulating cell survival. 5-Aminosalicylates such as mesalazine may reduce the development of colorectal cancer in ulcerative colitis, but the mechanisms of its chemopreventive action are not clear. Aims, To examine whether mesalazine affects the expression of c-Myc in human colon cancer cell lines. Methods, Human colon cancer cells were treated with vehicle or mesalazine (4 mm or 40 mm). We examined: (i) mRNA expression by gene array, (ii) protein expression by Western blotting and immunohistochemistry and (iii) apoptosis by Annexin V labelling. Results, Mesalazine significantly reduced expression of c-Myc mRNA and protein. Conclusions, Mesalazine downregulates gene and protein expression of c-Myc. The apoptotic and growth inhibitory effects of mesalazine are dose-dependent. Expression of c-Myc is significantly reduced by mesalazine 40 mm. [source] A tumour-associated DEAD-box protein, rck/p54 exhibits RNA unwinding activity toward c-myc RNAs in vitroGENES TO CELLS, Issue 8 2003Yukihiro Akao Background:, The rck/p54 protein of 473 amino acids belongs to the family of DEAD-box/putative RNA helicase proteins. DEAD-box proteins have been implicated in a wide variety of cellular processes ranging from the initiation of protein synthesis and ribosome biosynthesis to premRNA splicing by means of modifying the RNA structure. Our previous data suggested that rck/p54 positively affected the translation initiation of c-myc mRNA. Results:, The data obtained from morphological studies and surface plasmon resonance assays clearly indicated that the protein specifically bound to c-myc RNA transcripts (RNAs) and exhibited RNA unwinding activity toward c-myc RNAs in the presence of ATP in vitro. Experiments using a deletion mutant of rck/p54 retaining only its N-terminal 289 amino acids demonstrated that the deleted C-terminal 184 amino acid domain is involved in the RNA unwinding activity. Conclusion:, These findings strongly suggest that rck/p54 may play an important role in translation initiation by restructuring mRNAs even in the cell and contribute to carcinogenesis. [source] Inhibition of synoviocytes proliferation by two types of c-myc antisense oligodeoxynucleotidesINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2 2004Xinxin ZHAO Abstract Aim:, The c-myc proto-oncogene is over-expressed in synoviocytes from patients with rheumatoid arthritis (RA). For improving the inhibition of c-myc antisense oligodeoxynucleotides (AS ODN) on RA synoviocytes proliferation, we used two antisense sequences: one (antimyc-AUG AS ODN) targeting the initiation codon (AUG) and the next four codons on c-myc mRNA; another (antimyc-CRD AS ODN) targeting the coding region determinant (CRD) on c-myc mRNA to investigate if there was a difference on inhibiting synoviocytes proliferation. Methods:, Cultured human synoviocytes from patients with RA. The sequences were modified by phosphorothioates. Lipofectin was used as carrier. MTT assay was used to examine the inhibition of cell proliferation. Results:, Antimyc-AUG AS ODN and antimyc-CRD AS ODN both can inhibit synoviocytes proliferation dose-dependently. The maximum decrement of cell number was 40% at 2.5 µM and 48 h, 41.4% at 5 µM and 48 h, respectively. The action time of antimyc-AUG AS ODN inhibiting synoviocytes proliferation was earlier than that of antimyc-CRD AS ODN. ODN at high levels had non-sequence-specific cytotoxicity. Conclusions:, Both c-myc AS ODN are useful in inhibiting synoviocytes proliferation. [source] Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activityINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2005HIDEKI OUCHI Abstract Aim:, To clarify the mechanism of the anticancer effect of genistein, we examined the effect of genistein on telomerase activity in prostate cancer cells. We hypothesized that genistein may exert its anticancer effect by modifying telomerase activity in prostate cancer cells. Methods:, Prostate cancer (LNCaP) cells were cultured with genistein and the number of viable cells was counted. Growth medium was also collected to measure prostate-specific antigen (PSA) concentration. Polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay and reverse transcriptase (RT)-PCR analysis were performed to investigate telomerase activity and the expression of human telomerase reverse transcriptase (hTERT), c-myc and p21 mRNA. To examine the possibility that hTERT transcriptional activity is modulated by genistein, transient cell transfection studies were performed by using luciferase reporter assay. Telomere repeat amplification protocol (TRAP) assay and PCR analysis of hTERT were performed in androgen independent cells, DU-145. Results:, Cell growth of LNCaP was inhibited by genistein and PSA secretion was similarly reduced. In TRAP assay, the telomerase activity of LNCaP cells was reduced by genistein. Reverse transcriptase-PCR analysis revealed that the expression of hTERT and c-myc mRNA was down-regulated by genistein, whereas p21 mRNA increased in response to genistein. Luciferase reporter assay revealed that genistein reduced the transcriptional activity of hTERT. In DU-145 cells, telomerase activity and the expression of hTERT mRNA were also reduced by genistein. Conclusion:, The current study elucidated the molecular mechanism of cell growth inhibition by genistein. The antiproliferative effects of genistein seem to be exerted on the hTERT transcriptional activity via different molecular pathways. [source] | |||||||||||||