Identification of a MMTV insertion mutation within the coding region of the Fgf-3 protooncogene

被引:7
作者
Morris, DW
Dutra, JC
机构
[1] Department of Medical Pathology, University of California, Davis, Davis
[2] Department of Medical Pathology, Tupper Hall, University of California, Davis, Davis
关键词
D O I
10.1006/viro.1997.8794
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The Fgf-3 protooncogene (previously called int-e) is a target of proviral insertion mutations in mammary tumors induced by the mouse mammary tumor virus (MMTV). These insertion mutations result in the transcriptional activation of Fgf-3 which is not normally expressed in the adult mammary gland. Previous mapping studies of numerous Fgf-3 insertion mutations have failed to reveal any provirus integrations within the gene coding region. This finding is consistent with the hypothesis that oncogenesis occurs in this system as a consequence of up-regulation of Fgf-3 transcription, rather than from alterations of the gene product. During an analysis of a new cohort of tumors from the WXG-2 mouse strain, a breast tumor was identified which had a MMTV provirus integrated 24 bp upstream of the Fgf-3 stop codon. This insertion mutation generated a fusion transcript which was readily detectable in tumor RNA by RT-PCR. The predicted protein product of this fusion transcript is missing 8 aa of native sequence and contains an additional 8 aa of cryptic MMTV-encoded sequence. These data document the first exception to the generalization that the Fgf-3 coding region is not disrupted by MMTV insertion mutation. (C) 1997 Academic Press.
引用
收藏
页码:161 / 165
页数:5
相关论文
共 37 条
[1]   MMTV-induced mutations in mouse mammary tumors: Their potential relevance to human breast cancer [J].
Callahan, R .
BREAST CANCER RESEARCH AND TREATMENT, 1996, 39 (01) :33-44
[2]   ACTIVATION OF BOTH WNT-1 AND FGF-3 BY INSERTION OF MOUSE MAMMARY-TUMOR VIRUS DOWNSTREAM IN THE REVERSE ORIENTATION - A REAPPRAISAL OF THE ENHANCER INSERTION MODEL [J].
CLAUSSE, N ;
BAINES, D ;
MOORE, R ;
BROOKES, S ;
DICKSON, C ;
PETERS, G .
VIROLOGY, 1993, 194 (01) :157-165
[3]   MOUSE MAMMARY-TUMOR VIRUS ACTIVATES FGF-3/INT-2 LESS FREQUENTLY IN TUMORS FROM VIRGIN THAN FROM PAROUS MICE [J].
CLAUSSE, N ;
SMITH, R ;
CALBERGBACQ, CM ;
PETERS, G ;
DICKSON, C .
INTERNATIONAL JOURNAL OF CANCER, 1993, 55 (01) :157-163
[4]   DEVELOPMENT OF A MOUSE MAMMARY-TUMOR VIRUS-NEGATIVE MOUSE STRAIN - A NEW SYSTEM FOR THE STUDY OF MAMMARY CARCINOGENESIS [J].
COHEN, JC ;
TRAINA, VL ;
BREZNIK, T ;
GARDNER, M .
JOURNAL OF VIROLOGY, 1982, 44 (03) :882-885
[5]   ENDOGENOUS MAMMARY-TUMOR VIRUS-DNA VARIES AMONG WILD MICE AND SEGREGATES DURING INBREEDING [J].
COHEN, JC ;
VARMUS, HE .
NATURE, 1979, 278 (5703) :418-423
[6]   PROVIRAL INSERTIONS WITHIN THE INT-2 GENE CAN GENERATE MULTIPLE ANOMALOUS TRANSCRIPTS BUT LEAVE THE PROTEIN-CODING DOMAIN INTACT [J].
DICKSON, C ;
SMITH, R ;
BROOKES, S ;
PETERS, G .
JOURNAL OF VIROLOGY, 1990, 64 (02) :784-793
[7]   POTENTIAL ONCOGENE PRODUCT RELATED TO GROWTH-FACTORS [J].
DICKSON, C ;
PETERS, G .
NATURE, 1987, 326 (6116) :833-833
[8]   TUMORIGENESIS BY MOUSE MAMMARY-TUMOR VIRUS - PROVIRAL ACTIVATION OF A CELLULAR GENE IN THE COMMON INTEGRATION REGION INT-2 [J].
DICKSON, C ;
SMITH, R ;
BROOKES, S ;
PETERS, G .
CELL, 1984, 37 (02) :529-536
[9]   EXPRESSION, PROCESSING, AND PROPERTIES OF INT-2 [J].
DICKSON, C ;
FULLERPACE, F ;
KIEFER, P ;
ACLAND, P ;
MACALLAN, D ;
PETERS, G .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1991, 638 :18-26
[10]  
Dickson C, 1994, Cancer Treat Res, V71, P331