[Frontiers in Bioscience 2, d519-526-379, November 1, 1997]

	[Frontiers in Bioscience 2, d519-526-379, November 1, 1997] Reprints PubMed CAVEAT LECTOR
	ROLE OF MMTV INTEGRATION LOCUS CELLULAR GENES IN BREAST CANCER Rajeshwar Rao Tekmal, and Nagalakshmi Keshava Department of Gynecology and Obstetrics and Winship Cancer Center, Emory University School of Medicine, Atlanta, GA 30322-4710, USA Received 10/14/97 Accepted 10/17/97 5. INSERTIONAL MUTAGENESIS-MECHANISMS The important feature of the MMTV provirus is that the 3' LTR contains an open reading frame that encodes a superantigen (SAg), and, after reverse transcription and integration of the provirus into the genome, the viral superantigen is presented on the cell surface along with MHC class II molecules. The ability of an integrated provirus to activate the transforming potential of a flanking gene is in all cases mediated by the transcriptional control on the integration site and the transcriptional orientation of the provirus with respect to the cellular gene. These sequences are capable of initiating, enhancing and/or terminating transcription of host sequences, resulting in high levels of messenger RNAs encoding the intact protein or the production of aberrant transcripts encoding mutant proteins (3). Activation of the gene by the promoter insertion mechanism requires the integration of a provirus in the same transcriptional orientation as the target gene. Initiation of transcription occurs from the viral promoter in either the 5' or the 3' LTR, which replaces the function of the normal promoter. Viral deletions are frequently associated with activation by the promoter insertion in case the 3' LTR promoter is used. This results often in removal of the 5' LTR, suggesting that transcriptions driven by the 5' promoter and proceeding into the 3' LTR may negatively influence transcription from the 3' LTR-promoter (42). When the 5' LTR promoter is used, transcription results in the formation of fusion transcripts containing both viral and cellular sequences, due to frequent read-through at the 3' LTR polyadenylation site and subsequent splicing using the heteronuclear mRNA splice donor or cryptic splice donor sites.

[Frontiers in Bioscience 2, d519-526-379, November 1, 1997]
Reprints
PubMed
CAVEAT LECTOR

ROLE OF MMTV INTEGRATION LOCUS CELLULAR GENES IN BREAST CANCER

Rajeshwar Rao Tekmal, and Nagalakshmi Keshava

Department of Gynecology and Obstetrics and Winship Cancer Center, Emory University School of Medicine, Atlanta, GA 30322-4710, USA

Received 10/14/97 Accepted 10/17/97

5. INSERTIONAL MUTAGENESIS-MECHANISMS

The important feature of the MMTV provirus is that the 3' LTR contains an open reading frame that encodes a superantigen (SAg), and, after reverse transcription and integration of the provirus into the genome, the viral superantigen is presented on the cell surface along with MHC class II molecules. The ability of an integrated provirus to activate the transforming potential of a flanking gene is in all cases mediated by the transcriptional control on the integration site and the transcriptional orientation of the provirus with respect to the cellular gene. These sequences are capable of initiating, enhancing and/or terminating transcription of host sequences, resulting in high levels of messenger RNAs encoding the intact protein or the production of aberrant transcripts encoding mutant proteins (3). Activation of the gene by the promoter insertion mechanism requires the integration of a provirus in the same transcriptional orientation as the target gene. Initiation of transcription occurs from the viral promoter in either the 5' or the 3' LTR, which replaces the function of the normal promoter. Viral deletions are frequently associated with activation by the promoter insertion in case the 3' LTR promoter is used. This results often in removal of the 5' LTR, suggesting that transcriptions driven by the 5' promoter and proceeding into the 3' LTR may negatively influence transcription from the 3' LTR-promoter (42). When the 5' LTR promoter is used, transcription results in the formation of fusion transcripts containing both viral and cellular sequences, due to frequent read-through at the 3' LTR polyadenylation site and subsequent splicing using the heteronuclear mRNA splice donor or cryptic splice donor sites.