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.
Cancer Research Laboratory, University of California at Berkeley 94720, USA. tkbera@helix.nih.gov
T K
TK
Bera
T
T
Tsukamoto
D K
DK
Panda
T
T
Huang
R C
RC
Guzman
S I
SI
Hwang
S
S
Nandi
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)