Mammary tumor suppression by transforming growth factor beta 1 transgene expression.
In cell culture, type alpha transforming growth factor (TGF-alpha) stimulates epithelial cell growth, whereas TGF-beta 1 overrides this stimulatory effect and is growth inhibitory. Transgenic mice that overexpress TGF-alpha under control of the mouse mammary tumor virus (MMTV) promoter/enhancer exhibit mammary ductal hyperplasia and stochastic development of mammary carcinomas, a process that can be accelerated by administration of the chemical carcinogen 7,12-dimethylbenz[a]anthracene. MMTV-TGF-beta 1 transgenic mice display mammary ductal hypoplasia and do not develop mammary tumors. We report that in crossbreeding experiments involving the production of mice carrying both the MMTV-TGF-beta 1 and MMTV-TGF-alpha transgenes, there is marked suppression of mammary tumor formation and that MMTV-TGF-beta 1 transgenic mice are resistant to 7,12-dimethylbenz[a]anthracene-induced mammary tumor formation. These data demonstrate that overexpression of TGF-beta 1 in vivo can markedly suppress mammary tumor development.
Pierce
D F
DF
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-2175, USA.
Gorska
A E
AE
Chytil
A
A
Meise
K S
KS
Page
D L
DL
Coffey
R J
RJ
Moses
H L
HL
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000375:Aging; D000818:Animals; D003433:Crosses, Genetic; D004742:Enhancer Elements, Genetic; D005091:Exons; D005260:Female; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D016212:Transforming Growth Factor beta; D015127:9,10-Dimethyl-1,2-benzanthracene; D005914:Globins