Defective retrovirus insertion activates c-Ha-ras protooncogene in an MNU-induced rat mammary carcinoma.
Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number, of different cancers. here we report that the insertion of a defective retrovirus in the -1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3' end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection.
Bera
T K
TK
Cancer Research Laboratory, University of California at Berkeley 94720, USA. tkbera@helix.nih.gov
Tsukamoto
T
T
Panda
D K
DK
Huang
T
T
Guzman
R C
RC
Hwang
S I
SI
Nandi
S
S
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology*; D005091:Exons; D005260:Female; D015752:Genes, env; D011905:Genes, ras; D007438:Introns; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D008770:Methylnitrosourea; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D011994:Recombinant Proteins; D008770:Methylnitrosourea; D016283:Proto-Oncogene Proteins p21(ras)