Activation of myc Gene Family in Human Lung Carcinomas and during Heterotransplantation into Nude Mice1 (original) (raw)
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Involvement of Myc targets in c-myc and N-myc induced human tumors
Oncogene, 1998
The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the speci®c DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), a-prothymosin and Cdc25A. In this study we examined the involvement of c-Myc target genes in human oncogenesis induced by c-myc or N-myc. In MCF-7 breast cancer cells, the induction of c-myc expression by estrogen was followed by the induction of all the Myc targets that we examined, indicating that those genes can serve as c-Myc targets in human oncogenesis. Moreover, in breast tumors exhibiting c-myc overexpression, several Myc targets were also overexpressed. A clear correlation between the expression of c-myc and its targets was also detected in Burkitt's lymphomas, which involve a speci®c translocation of c-myc gene, but not in other lymphoma cells. Yet, in cells derived from a neuronal origin the pattern of expression of Myc targets was more complex. In a neuroepithelioma cell line that overexpresses c-myc, only some targets were expressed. In addition in neuroblastomas, in which N-myc is ampli®ed and overexpressed, only ODC was overexpressed in all cell lines, while all other target genes were expressed in only some of the cell lines. The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identi®ed originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell speci®c factors are also needed for transcription of the target genes.
International Journal of Cancer, 1989
In a small-cell lung carcinoma (SCLC) tumor specimen as well as in 3 cell lines derived from SCLC biopsies obtained from the same patient at successive times during the clinical course, either the N-myc gene or the c-myc gene appeared to be amplified and expressed. The initial tumor specimen, a lymph-node metastasis, was amplified for N-myc, as was the cell line GLC-14 derived from this metastasis. The cell lines GLC-16 and GLC-19, derived from recurrent primary tumor biopsies after a complete remission, were amplified for cmyc. This finding implies independent amplification events and supports the idea that the amplification of myc genes is probably a secondary event correlated with tumor progression. Although all 3 cell lines could be classified as classic SCLC cell lines according to their histological characteristics, GLC-16 and GLC-I9 clearly possess, in their c-myc amplification and derivation from therapy-resistant tumor cells, features of variant SCLC lines. This may question the significance of the classidvariant classification.
Cancer research, 1985
Cell line SW 613-S, derived from a human breast carcinoma, contained double minute chromosomes (DMs) but lost them progressively upon in vitro cultivation. These cells were tumorigenic in nude mice. Cell lines were derived from the tumors and were found to have a high DM content. In three such cell lines, DMs were stably maintained upon in vitro cultivation, whereas in another they were progressively lost. We found that the c-myc oncogene is amplified 5- to 10-fold in SW 613-S and 20- to 90-fold in the different cell lines derived from the tumors. At least part of the additional c-myc copies were found associated with a purified DM fraction. In cell lines which lost the DMs during in vitro passages, the level of amplification was maintained. In situ hybridization experiments indicated that this loss was compensated by the acquisition of copies of the c-myc gene integrated into a chromosome. No major rearrangement of the amplified c-myc gene was detected. The amount of c-myc messenge...
MYC oncogenes and human neoplastic disease
Oncogene, 1999
c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we first summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite different roles in vivo. This concept necessarily lies at the heart of the
Amplification of the C-MYC Oncogene in Non-small Cell Lung Cancer
Tumori Journal, 1999
Fresh non-small cell lung carcinoma surgical specimens were taken from 17 patients and 3 controls and screened for genetic abnormalities of the c-myc oncogene. Southern blot hybridization analysis demonstrated twoto fivefold amplification of the c-myc gene in 10 cases, i.e., 7 of 13 epidermoid lung carci-nomas, 2 of 3 adenocarcinomas and 1 of 1 osteogenic sarcoma metastatic to the lung. Twoto fivefold amplification was observed in tissues from stage Ill and IV epidermoid carcinomas and adenocarcinomas of the lung. A correlation between cancer stage and c-myc gene amplification was found.
Contributions of Myc to tumorigenesis
Biochimica Et Biophysica Acta-reviews on Cancer, 2002
Despite intensive research, the mechanisms by which deregulation of myc gene expression contributes to tumorigenesis are still not fully resolved and many aspects are still enigmatic. Several recent reviews, including one published in this series a few months ago, have summarized recent progress in our understanding of the biochemistry of Myc proteins [Eisenmann, Genes Dev. (2001) in press; Amati et al., Biochim. Biophys. Acta 1471 ]. Also, the evidence documenting a central role of Myc proteins in human tumorigenesis has been extensively reviewed [Henriksson and Lu « scher, Cancer Res. 68 (1996) 109^182]. In this article, we will argue that current progress allows us to present testable hypotheses on how Myc affects specific properties of transformed cells. ß
Localization of amplified c-myc and n-myc in small cell lung cancer cell lines
Cancer Genetics and Cytogenetics, 1989
In this stud',. 12 small cell lung cancer cell hnes ~ere tested for amphflcatmn of mvc oncogenes the locatmn of amphf3ed sequences and the poss~ble correlatmn between number of dram and degree oJ amphflcatmn m dmm-contmnmg hnes C-myc appeared to be amphhed m four cell hnes. and N-m~ c amphflcatmn was detected m two cell hnes No amphf~catmn of Lmvc was found The degree of amph~catmn m the different cell hnes varied bet~ een 20 x and lOOX The cell hnes v~lth mvc amphflcatmn appeared to contmn numerous dram although m one cell hne the~ occurred m only 10% of the cells The other cells m th~s hne contained a homogeneousl~ staining regmn (HSR) In s~tu hvbndlzatmn was carried out to find the locatmn of the amphflcatmn In four cell hnes the amphOed myc genes were found to be located on the dram In the cell hne wJth the HSR m most cells and dram m a minority of its cells amphflcatmn was round both at the HSR and on the dram In one cell hne the myc sequences seemed to be dispersed through the genome The ratm between the m erage number of dram per cell and the degree of amphflcatmn dzd not varv canslderabl~ bet~een the cell hnes ~ zth one exceptmn In that cell hne the number of dram exceeded the number of mvc sequences b~ about one order ot magmtude Apparently. the populatmn of dram m th~s cell ~as heterogeneous and amphf3ed m~c genes uere onh present on a subpopulatmn present Occurrence of dram can be conmdered as a cytogenetic lndmatlon of gene
Over-expression and amplification of the c-myc gene in human urothelial carcinoma
International Journal of Cancer, 1999
To understand the mechanisms underlying increased expression of Myc protein in human urinary bladder cancer, expression of c-myc mRNA and the copy number of the c-myc gene were determined. Expression of mRNA was measured by quantitative RT-PCR in 40 urothelial carcinomas and in 18 histologically normal mucosae. Mean expression in tumors was significantly increased (3.23 ؎ 2.63 AU vs. 1.90 ؎ 0.95 AU, p F 0.023) and exceeded the highest level in normal mucosa in 15 (37.5%) tumors. The c-myc gene copy number was higher than in leukocytes and normal bladder mucosa in 14 of 40 tumors, but only 3 among these showed a more than 4-fold increase indicative of gene amplification. Most, but not all, tumors with elevated expression displayed an increased gene copy number (p F 0.0001). In line with other studies of the protein level, no significant association either of c-myc mRNA over-expression or of increased gene copy number with tumor stage or grade was observed. The data indicate that elevated mRNA expression as a consequence of increases in c-myc gene copy number often underlies Myc protein overexpression in bladder cancer. This increase may be a consequence of, most frequently, chromosome 8q gain and, occasionally, gene amplification, while in some tumors deregulation of mRNA expression occurs without evident changes in the c-myc gene copy number.