Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus.

DeFeo, D; Gonda, Matthew A.; Young, Howard A.; Chang, Esther H.; Lowy, Douglas R.; Scolnick, Edward M.; Ellis, Ronald W.

doi:10.1073/pnas.78.6.3328

Cited by 270 publications

(95 citation statements)

References 36 publications

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“…Blair et al first demonstrated that the mouse mos proto-oncogene can transform NIH 3T3 cells when placed under the control of retroviral regulatory elements (6). Similar results have subsequently been obtained with other proto-oncogenes such as H-ras-J (7,9) and sis (8,12).…”

supporting

confidence: 62%

ras gene Amplification and malignant transformation.

Pulciani¹,

Santos²,

Long³

et al. 1985

Mol. Cell. Biol.

189

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Morphologic transformation of NIH 3T3 mouse cells occurs upon transfection of these cells with large amounts (greater than or equal to 10 micrograms) of recombinant DNA molecules carrying the normal human H-ras-1 proto-oncogene. We provide experimental evidence indicating that transformation of these NIH 3T3 cells results from the combined effect of multiple copies of the H-ras-1 proto-oncogene rather than from spontaneous mutation of one of the transfected H-ras-1 clones (E. Santos, E.P. Reddy, S. Pulciani, R.J. Feldman, and M. Barbacid, Proc. Natl. Acad. Sci. USA 80:4679-4683, 1983). Levels of H-ras-1 RNA and p21 expression are highly elevated in the NIH 3T3 transformants, and in those cases examined, these levels correlate with the malignant properties of these cells. We have also investigated the presence of amplified ras genes in a variety of human carcinomas. In 75 tumor biopsies, we found amplification of the human K-ras-2 locus in one carcinoma of the lung. These results indicate that ras gene amplification is an alternative pathway by which ras genes may participate in the development of human neoplasia.

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supporting

confidence: 62%

ras gene Amplification and malignant transformation.

Pulciani¹,

Santos²,

Long³

et al. 1985

Mol. Cell. Biol.

189

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“…These subtle changes are sufficient to confer transforming properties to the ras proteins (16,25,31). There is evidence that a substantial increase in normal rcas p21 expression can be transforming as well (1).…”

mentioning

confidence: 98%

Antibody of predetermined specificity to a carboxy-terminal region of H-ras gene products inhibits their guanine nucleotide-binding function.

Srivastava¹,

Lacal²,

Reynolds³

et al. 1985

Mol. Cell. Biol.

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The high prevalence of ras oncogenes in human tumors has given increasing impetus to efforts aimed at elucidating the structure and function of their p21 products. To identify functionally important domains of the p21 protein, antibodies were generated against synthetic peptides corresponding to various regions of the protein. Antibodies directed against a synthetic peptide fragment corresponding to amino acid residues 161 to 176 in the carboxy-terminal region of the H-ras-encoded p21 molecule specifically recognized H-ras-encoded p21 proteins. This antibody was also shown to strikingly and specifically inhibit the guanine nucleotide-binding function of the p21 protein. The inability of p21 protein to bind guanine nucleotides was associated with a lack of autophosphorylation or GTPase activities. These studies suggest that a region toward its carboxy terminus is directly or indirectly involved in the guanine nucleotide-binding function of the p21 molecule.

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“…This truncated EGR receptor is constitutively active, and therefore cells expressing v-erb undergo a chronic EGF stimulation (Lax et al, 1985). An example of a viral oncogene coding for a critical component of growth signal transduction pathways is represented by Ha-MuSV (homologue to the cellular gene Ha-ras) (DeFeo et al, 1981), encoded by the Harvey murine sarcoma virus. An example of a viral oncogene encoding a transcription factor is provided by REV-T, homologous to a member of the NFkB protein family (Wilhelmsen et al, 1984;Lee et al, 1991), encoded by the Reticuloendotheliosis virus.…”

Section: Gain Of Function In the Pathway Of Malignant Transformation:mentioning

confidence: 99%

Epidemiology and molecular pathology at crossroads to establish causation: molecular mechanisms of malignant transformation

Bocchetta

Carbone

2004

Oncogene

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Epidemiology is a very reliable science for the identification of carcinogens. Epidemiological studies require that the effect, cancer in this case, has already occurred, when of course it would be more desirable to identify potential carcinogenic substances at an earlier stage before they have caused a large number of malignancies and thus become identifiable by epidemiological studies. In the past 30 years, molecular pathology (which includes chemistry, biochemistry, molecular biology, molecular virology, molecular genetics, epigenetics, genomics, proteomics, and other molecular-based approaches) has identified some key alterations that are required for cellular transformation and malignancy. Agents that specifically interfere with some of these mechanisms are suspected human carcinogens. It can be stated that tumor formation requires the following steps: (1) inactivation of Rb and p53 cellular pathways; (2) activation of Ras and/or other growth promoting pathways; (3) inactivation of phosphatase 2A that causes changes in the phosphorylation and activity of several cellular proteins; (4) evasion of apoptosis; (5) telomerase activation or alternative mechanisms of cellular immortalization; (6) angiogenic activity; and (7) the ability to invade surrounding tissues and to metastasize. Here, we review the molecular mechanisms of cellular transformation. The integration of this knowledge with classical epidemiology and animal studies should permit a more rapid and accurate identification of human carcinogens.

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Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus.

Cited by 270 publications

References 36 publications

ras gene Amplification and malignant transformation.

ras gene Amplification and malignant transformation.

Antibody of predetermined specificity to a carboxy-terminal region of H-ras gene products inhibits their guanine nucleotide-binding function.

Epidemiology and molecular pathology at crossroads to establish causation: molecular mechanisms of malignant transformation

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