The int-2 gene product acts as an epithelial growth factor in transgenic mice.
The induction of mammary tumors by mouse mammary tumor virus (MMTV) is thought to occur through proviral activation of one or more cellular genes. One of these, int-2, encodes a 27 kd protein which exhibits striking homology to the basic fibroblast growth factor family. To assess directly the role of the int-2 protein in cell proliferation, we have established transgenic mice which carry the int-2 gene driven by the MMTV promoter/enhancer. Expression of the int-2 gene in female transgenic mice results in pronounced mammary gland hyperplasia. Interestingly, expression of the MMTV-int-2 transgene in the prostate gland of male carriers results in a benign, but dramatic, epithelial hyperplasia similar to benign prostatic hypertrophy (BPH), a common but poorly understood disorder in human populations. Together, these results indicate that the int-2 product can act as a potent growth factor in these epithelial tissues.
Muller
W J
WJ
Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA 02115.
Lee
F S
FS
Dickson
C
C
Peters
G
G
Pattengale
P
P
Leder
P
P
D000818:Animals; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors; D015870:Gene Expression; D005822:Genetic Vectors; D006133:Growth Substances / Q000235:genetics*; D008297:Male; D008321:Mammary Glands, Animal / Q000382:microbiology / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008822:Mice, Transgenic; D011467:Prostate / Q000382:microbiology / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000382:microbiology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D015183:Restriction Mapping
D004279:DNA, Viral; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors