PMID- 15340078
OWN - NLM
STAT- MEDLINE
DCOM- 20041007
LR  - 20220224
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 24
IP  - 18
DP  - 2004 Sep
TI  - Role of F-box protein betaTrcp1 in mammary gland development and tumorigenesis.
PG  - 8184-94
AB  - The F-box protein betaTrcp1 controls the stability of several crucial regulators 
      of proliferation and apoptosis, including certain inhibitors of the NF-kappaB 
      family of transcription factors. Here we show that mammary glands of 
      betaTrcp1(-/-) female mice display a hypoplastic phenotype, whereas no effects on 
      cell proliferation are observed in other somatic cells. To investigate further 
      the role of betaTrcp1 in mammary gland development, we generated transgenic mice 
      expressing human betaTrcp1 targeted to epithelial cells under the control of the 
      mouse mammary tumor virus (MMTV) long terminal repeat promoter. Compared to 
      controls, MMTV betaTrcp1 mammary glands display an increase in lateral ductal 
      branching and extensive arrays of alveolus-like protuberances. The mammary 
      epithelia of MMTV betaTrcp1 mice proliferate more and show increased NF-kappaB 
      DNA binding activity and higher levels of nuclear NF-kappaB p65/RelA. In 
      addition, 38% of transgenic mice develop tumors, including mammary, ovarian, and 
      uterine carcinomas. The targeting of betaTrcp1 to lymphoid organs produces no 
      effects on these tissues. In summary, our results support the notion that 
      betaTrcp1 positively controls the proliferation of breast epithelium and indicate 
      that alteration of betaTrcp1 function and expression may contribute to malignant 
      behavior of breast tumors, at least in part through NF-kappaB transactivation.
FAU - Kudo, Yasusei
AU  - Kudo Y
AD  - Department of Pathology and NYU Cancer Institute, New York University School of 
      Medicine, NY 10016, USA.
FAU - Guardavaccaro, Daniele
AU  - Guardavaccaro D
FAU - Santamaria, Patricia G
AU  - Santamaria PG
FAU - Koyama-Nasu, Ryo
AU  - Koyama-Nasu R
FAU - Latres, Esther
AU  - Latres E
FAU - Bronson, Roderick
AU  - Bronson R
FAU - Yamasaki, Lili
AU  - Yamasaki L
FAU - Pagano, Michele
AU  - Pagano M
LA  - eng
GR  - R01 CA079646/CA/NCI NIH HHS/United States
GR  - R01-GM57587/GM/NIGMS NIH HHS/United States
GR  - R01 GM057587/GM/NIGMS NIH HHS/United States
GR  - R01-CA76584/CA/NCI NIH HHS/United States
GR  - R01 CA076584/CA/NCI NIH HHS/United States
GR  - R01-CA79646/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Recombinant Proteins)
RN  - 0 (beta-Transducin Repeat-Containing Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA/genetics
MH  - Female
MH  - Gene Targeting
MH  - Humans
MH  - Mammary Glands, Animal/abnormalities/*growth & development
MH  - Mammary Neoplasms, Experimental/*etiology/genetics/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Phenotype
MH  - Recombinant Proteins/genetics/metabolism
MH  - beta-Transducin Repeat-Containing Proteins/deficiency/genetics/*physiology
PMC - PMC515055
EDAT- 2004/09/02 05:00
MHDA- 2004/10/08 09:00
PMCR- 2004/09/01
CRDT- 2004/09/02 05:00
PHST- 2004/09/02 05:00 [pubmed]
PHST- 2004/10/08 09:00 [medline]
PHST- 2004/09/02 05:00 [entrez]
PHST- 2004/09/01 00:00 [pmc-release]
AID - 24/18/8184 [pii]
AID - 0727-04 [pii]
AID - 10.1128/MCB.24.18.8184-8194.2004 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2004 Sep;24(18):8184-94. doi: 10.1128/MCB.24.18.8184-8194.2004.