Transforming growth factor-beta1 is a new form of tumor suppressor with true haploid insufficiency.
Components of the transforming growth factor-beta (TGF-beta) signal pathway function as classic tumor suppressors, but the role of the TGF-betas themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-beta1 gene express only 10-30% of wild-type TGF-beta1 protein levels. Although grossly normal, these mice have a subtly altered proliferative phenotype, with increased cell turnover in the liver and lung. Treatment of these mice with chemical carcinogens resulted in enhanced tumorigenesis when compared with wild-type littermates. However, tumors in the heterozygous mice did not lose the remaining wild-type TGF-beta1 allele, indicating that the TGF-beta1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis.
Tang
B
B
Laboratory of Cell Regulation and Carcinogenesis (formerly Laboratory of Chemoprevention), National Cancer Institute, Bethesda, Maryland 20892-5055, USA.
Böttinger
E P
EP
Jakowlew
S B
SB
Bagnall
K M
KM
Mariano
J
J
Anver
M R
MR
Letterio
J J
JJ
Wakefield
L M
LM
D000818:Animals; D017209:Apoptosis; D015197:Carcinogenicity Tests; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division; D018390:Gene Targeting; D016147:Genes, Tumor Suppressor; D008099:Liver / Q000166:cytology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D016212:Transforming Growth Factor beta