PMID- 12388754
OWN - NLM
STAT- MEDLINE
DCOM- 20030702
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 13
IP  - 10
DP  - 2002 Oct
TI  - Perturbation of beta1-integrin function in involuting mammary gland results in 
      premature dedifferentiation of secretory epithelial cells.
PG  - 3521-31
AB  - To study the mechanism of beta1-integrin function in vivo, we have generated 
      transgenic mouse expressing a dominant negative mutant of beta1-integrin under 
      the control of mouse mammary tumor virus (MMTV) promoter (MMTV-beta1-cyto). 
      Mammary glands from MMTV-beta1-cyto transgenic females present significant growth 
      defects during pregnancy and lactation and impaired differentiation of secretory 
      epithelial cells at the onset of lactation. We report herein that perturbation of 
      beta1-integrin function in involuting mammary gland induced precocious 
      dedifferentiation of the secretory epithelium, as shown by the premature decrease 
      in beta-casein and whey acidic protein mRNA levels, accompanied by inactivation 
      of STAT5, a transcription factor essential for mammary gland development and 
      up-regulation of nuclear factor-kappaB, a negative regulator of STAT5 signaling. 
      This is the first study demonstrating in vivo that cell-extracellular matrix 
      interactions involving beta1-integrins play an important role in the control of 
      milk gene transcription and in the maintenance of the mammary epithelial cell 
      differentiated state.
FAU - Faraldo, Marisa M
AU  - Faraldo MM
AD  - Unite Mixte Recherche 144, Centre National de la Recherche Scientifique-Institut 
      Curie, Section de Recherche, 75248 Paris, France.
FAU - Deugnier, Marie-Ange
AU  - Deugnier MA
FAU - Tlouzeau, Sylvie
AU  - Tlouzeau S
FAU - Thiery, Jean Paul
AU  - Thiery JP
FAU - Glukhova, Marina A
AU  - Glukhova MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (CD4 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Integrin beta1)
RN  - 0 (Milk Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - CD4 Antigens/genetics/metabolism
MH  - Cell Differentiation/*physiology
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Epithelial Cells/cytology/*physiology
MH  - Female
MH  - Genes, Reporter
MH  - Integrin beta1/genetics/*metabolism
MH  - Janus Kinase 2
MH  - Lactation/*physiology
MH  - Mammary Glands, Animal/cytology/*physiology
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Milk Proteins/genetics
MH  - NF-kappa B/metabolism
MH  - Pregnancy
MH  - Promoter Regions, Genetic
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - *Proto-Oncogene Proteins
MH  - RNA, Messenger/metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - STAT5 Transcription Factor
MH  - Signal Transduction/physiology
MH  - Trans-Activators/genetics/metabolism
PMC - PMC129963
EDAT- 2002/10/22 04:00
MHDA- 2003/07/03 05:00
PMCR- 2002/12/01
CRDT- 2002/10/22 04:00
PHST- 2002/10/22 04:00 [pubmed]
PHST- 2003/07/03 05:00 [medline]
PHST- 2002/10/22 04:00 [entrez]
PHST- 2002/12/01 00:00 [pmc-release]
AID - 1972 [pii]
AID - 10.1091/mbc.e02-02-0086 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2002 Oct;13(10):3521-31. doi: 10.1091/mbc.e02-02-0086.