TRANSFORMING GROWTH-FACTOR-BETA-1 IS A NEW FORM OF TUMOR-SUPPRESSOR WITH TRUE HAPLOID INSUFFICIENCY

TANG BW BOTTINGER EP JAKOWLEW SB BAGNALL KM MARIANO J ANVER MR LETTERIO JJ WAKEFIELD LM

Bw. Tang et al., TRANSFORMING GROWTH-FACTOR-BETA-1 IS A NEW FORM OF TUMOR-SUPPRESSOR WITH TRUE HAPLOID INSUFFICIENCY, Nature medicine, 4(7), 1998, pp. 802-807

45

INGLESE

Article

Medicine, Research & Experimental",Biology,"Cell Biology

Nature medicine → ACNP

1078-8956

4

7

1998

802 - 807

ISI

1078-8956(1998)4:7<802:TGIANF>2.0.ZU;2-C

Components of the transforming growth factor-beta (TGF-beta) signal pa thway function as classic tumor suppressors, but the role of the TGF-b eta s themselves is less clear. Here we show that mice heterozygous fo r deletion of the TGF-beta 1 gene express only 10-30% of wild-type TGF -beta 1 protein levels. Although grossly normal, these mice have a sub tly altered proliferative phenotype, with increased cell turnover in t he liver and lung. Treatment of these mice with chemical carcinogens r esulted in enhanced tumorigenesis when compared with wild-type litterm ates. However, tumors in the heterozygous mice did not lose the remain ing wild-type TGF-beta 1 allele, indicating that the TCF-beta 1 ligand is a new form of tumor suppressor that shows true haploid insufficien cy in its ability to protect against tumorigenesis.