TY - JOUR
T1 - Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth
AU - Schreiber-Agus, Nicole
AU - Meng, Yong
AU - Hoang, Tin
AU - Hou, Harry
AU - Ghen, Ken
AU - Greenberg, Roger
AU - Cordon-Cardo, Carlos
AU - Leet, Han Woong
AU - Depinho, Ronald A.
PY - 1998/6/4
Y1 - 1998/6/4
N2 - Mxi1 belongs to the Mad (Mxi1) family of patients, which function as potent antagonists of Myc oncoproteins. This antagonism relates partly to their ability to compete with Myc for the protein Max and for consensus DNA binding sites and to recruit transcriptional co-repressors. Mad(Mxi1) proteins have been suggested to be essential in cellular growth control and/or in the induction and maintenance of the differentiated state. Consistent with these roles, mxi1 may be the tumour-suppressor gene that resides at region 24-26 of the long arm of chromosome 10. This region is a cancer hotspot, and mutations here may be involved in several cancers, including prostate adenocarcinoma. Here we show that mice lacking Mxi1 exhibitor progressive, multisystem abnormalities. These mice also show increased susceptibility to tumorigenesis either following carcinogen treatment or when also deficient in Ink4a. This cancer-prone phenotype may correlate with the enhanced ability of several mxi1-deficient cell types, including prostatic epithelium, to proliferate. Our results show that Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner.
AB - Mxi1 belongs to the Mad (Mxi1) family of patients, which function as potent antagonists of Myc oncoproteins. This antagonism relates partly to their ability to compete with Myc for the protein Max and for consensus DNA binding sites and to recruit transcriptional co-repressors. Mad(Mxi1) proteins have been suggested to be essential in cellular growth control and/or in the induction and maintenance of the differentiated state. Consistent with these roles, mxi1 may be the tumour-suppressor gene that resides at region 24-26 of the long arm of chromosome 10. This region is a cancer hotspot, and mutations here may be involved in several cancers, including prostate adenocarcinoma. Here we show that mice lacking Mxi1 exhibitor progressive, multisystem abnormalities. These mice also show increased susceptibility to tumorigenesis either following carcinogen treatment or when also deficient in Ink4a. This cancer-prone phenotype may correlate with the enhanced ability of several mxi1-deficient cell types, including prostatic epithelium, to proliferate. Our results show that Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner.
UR - http://www.scopus.com/inward/record.url?scp=0032482421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032482421&partnerID=8YFLogxK
U2 - 10.1038/31008
DO - 10.1038/31008
M3 - Article
C2 - 9624006
AN - SCOPUS:0032482421
SN - 0028-0836
VL - 393
SP - 483
EP - 487
JO - Nature
JF - Nature
IS - 6684
ER -