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Showing papers by "Kari Alitalo published in 1985"


Journal ArticleDOI
TL;DR: The finding of amplification of a cellular oncogene (c-myc) in fresh AML cells containing double minute chromosomes suggests that clonal evolution of some leukaemia cell populations may involve selection for increased dosage of oncogenes.

86 citations


Journal ArticleDOI
TL;DR: In this paper, it was shown that Amplified copies of oncogenes may or may not be associated with chromosomal abnormalities signifying DNA amplification: double minute chromosomes and homogeneously staining chromosomal regions.
Abstract: Regulatory or structural alterations of cellular oncogenes have been implicated in the causation of various cancers. Oncogene alteration by point mutations can result in a protein product with strongly enhanced oncogenic potential. Aberrant expression of cellular oncogenes may be due to tumor-specific chromosomal translocations that dysregulate the normal functions of a proto-oncogene. Amplification of cellular oncogenes can also augment their expression by increasing the amount of DNA template available for the production of mRNA. It appears that amplification of certain oncogenes is a common correlate of the progression of some tumours and also occurs as a rare sporadic event affecting various oncogenes in different types of cancer. Amplified copies of oncogenes may or may not be associated with chromosomal abnormalities signifying DNA amplification: double minute chromosomes and homogeneously staining chromosomal regions. Amplified oncogenes, whether sporadic or tumour type-specific, are expressed at elevated levels, in some cases in cells where their diploid forms are normally silent. Increased dosage of an amplified oncogene may contribute to the multistep progression of at least some cancers.

73 citations


Journal Article
TL;DR: Two of six cell lines, both of which were small cell carcinomas, showed about a 20-fold amplification of the c-myc oncogene, which confirms and extends earlier findings on c- myc amplification in small cell lung cancer.
Abstract: We have examined a panel of human lung cancer cell lines for amplification and expression of the c-myc, N-myc, and c-myb oncogenes. The cell lines analyzed represent various histopathological types of lung cancer: small cell carcinoma with neuroendocrine properties; squamous cell carcinoma with epithelial markers; and large cell carcinoma with a mixed neuroendocrine-epithelial phenotype. Two of six cell lines, both of which were small cell carcinomas, showed about a 20-fold amplification of the c-myc oncogene. In both cell lines, the amplification is accompanied by an enhanced expression of c-myc. The N-myc or c-myb genes were not amplified in any of the cell lines, nor were they expressed in detectable amounts. The results confirm and extend earlier findings on c-myc amplification in small cell lung cancer.

72 citations


Journal ArticleDOI
23 May 1985-Nature
TL;DR: It is shown that cells of SEWA lines carrying DMs, HSRs or CMs contain amplified copies of the proto-oncogene c- myc and enhanced levels of c-myc messenger RNA and c-Myc protein.
Abstract: SEWA tumour cells are derived from an osteosarcoma induced in an A.SW mouse by infection with polyoma virus1. Cytogenetic analyses have revealed three different characteristic chromosomal abnormalities diagnostic for the presence of amplified genes: ‘double minutes’ (DMs), homogeneously staining chromosomal regions (HSRs) and C-bandless chromosomes (CMs; for review see ref. 2). DMs may undergo fluctuation in number depending on the conditions in which the cells grow. Their number usually increases after injection of cells into a mouse and often is reduced to undetectable levels when the cells are explanted back into tissue culture; when the cells are re-introduced into the mouse, they again acquire multiple DMs3. We show here that cells of SEWA lines carrying DMs, HSRs or CMs contain amplified copies of the proto-oncogene c-myc and enhanced levels of c-myc messenger RNA and c-myc protein. DMs or CMs are the sites of c-myc amplification in two different SEWA lines.

67 citations


Journal ArticleDOI
TL;DR: The results suggest that the amplified c-myc appeared first as DMs and was subsequently transposed to engender HSRs on an X chromosome, suggesting that the initial COLO 320 tumor cell may have acquired two “early replicating” X chromosomes and lost the “late replicating" X.
Abstract: Cell lines (COLO 320 DM and COLO 320 HSR), established from a human neuroendocrine tumor, contain an amplified cellular oncogene (c-myc). We have previously shown that the homogeneously staining regions (HSRs) of a marker chromosome in the COLO 320 HSR cells that evolved in culture from COLO 320 DM cells contain amplified c-myc. Molecular hybridization in situ has now been used to demonstrate that the HSRs are on both arms of what was once an X chromosome. We also show that amplified c-myc copies are present in the isolated double minute chromosomes (DMs) of the COLO 320 DM cells that were characteristic of the tumor cells initially established from the patient. The results suggest that the amplified c-myc appeared first as DMs and was subsequently transposed to engender HSRs on an X chromosome. The initial COLO 320 tumor cell may have acquired two "early replicating" (i.e., active) X chromosomes and lost the "late replicating" (i.e., inactive) X.

49 citations


Journal ArticleDOI
TL;DR: A new mutant strain that has greatly increased ornithine decarboxylase activity is isolated from an arginase-deficient polyamine-dependent Chinese hamster ovary cell line, which enables the cells to decar boxylate lysine into cadaverine (diaminopentane) that is further converted into N-(3-aminopropyl)cadaverines and N,N'-bis(3-amino-bis-cada

44 citations


Journal ArticleDOI
TL;DR: It is suggested that c-myb was amplified in situ in a chromosomal segment (6q22-24) that became a part of the marker chromosome, possibly through isochromosome formation followed by duplication, and without the extrachromosomal intermediate form of double minute chromosomes.

16 citations


Journal ArticleDOI
TL;DR: Results suggest a relationship between membrane-associated p36 and the cytoskeletal fibres that terminate at the plasma membrane in PtK2 cells and show for the first time a drug-induced redistribution of p36.

12 citations



Journal ArticleDOI
TL;DR: Cleavage fragments of p110gag‐myc and p58myc showed the presence of a p15 cleavage site within the myc‐specific region, which is missing in deletion mutants of MC29 virus.
Abstract: Myc-related proteins were precipitated from MC29 virus-transformed cells (PR-2) and from OK10 virus-transformed cells (9C) by anti-gag and anti-myc sera. Immunoprecipitates were cleaved with the avian retroviral protease p15 and the cleavage products analyzed in SDS-PAGE. Cleavage fragments of p110gag-myc (product of MC29 virus) and p58myc (product of OK10 virus) showed the presence of a p15 cleavage site within the myc-specific region. The site is missing in deletion mutants of MC29 virus.

1 citations


Book ChapterDOI
01 Jan 1985
TL;DR: It appears that the amplification of certain oncogenes is both a common correlate of the progression of some tumors and occurs as a rare sporadic event affecting various oncogenees in different types of cancer.
Abstract: Regulatory or structural alterations of cellullar oncogenes have been implicated in the causation of various forms of cancer. Oncogene alteration by point mutations can result in a protein product with strongly enhanced tumorigenic potential. Aberrant expression of cellular oncogenes may result from tumor-specific chromosomal translocations that dysregulate the normal function of a proto-oncogene. The amplification of cellular oncogenes can also enhance their expression by increasing the amount of DNA template available for the production of mRNA. It appears that the amplification of certain oncogenes is both a common correlate of the progression of some tumors and occurs as a rare sporadic event affecting various oncogenes in different types of cancer. Amplified copies of oncogenes may or may not be associated with chromosomal abnormalities that signify DNA amplification.