PMID- 21933656
OWN - NLM
STAT- MEDLINE
DCOM- 20120124
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 179
IP  - 5
DP  - 2011 Nov
TI  - Targeted expression of GLI1 in the salivary glands results in an altered 
      differentiation program and hyperplasia.
PG  - 2569-79
LID - 10.1016/j.ajpath.2011.07.033 [doi]
AB  - Hedgehog (Hh) signaling is a regulator of salivary gland morphogenesis, but its 
      role in postnatal glands has only recently begun to be addressed. To examine the 
      effects of deregulated Hh signaling in the salivary gland, we expressed the Hh 
      effector protein GLI1, in salivary epithelial cells using both cytokeratin 5 and 
      mouse mammary tumor virus (MMTV) transgenic systems. Ectopic pathway activation 
      resulted in restrained acinar differentiation, formation of cystic lesions, and 
      prominent appearance of ductal structures. Moreover, induced expression of GLI1 
      aids the formation of hyperplastic lesions, which closely resemble GLI1-induced 
      changes in murine skin and mammary glands, suggesting that GLI1 targets cells 
      with similar characteristics in different tissues. Furthermore, GLI1-expressing 
      salivary epithelial cells are actively dividing, and GLI1-induced lesions are 
      proliferative, an incident accompanied by enhanced expression of the Hh target 
      genes, cyclin D1, and Snail. GLI1-induced salivary lesions regress after 
      transgene withdrawal and become histologically normalized. Taken together, our 
      data reveal the ability of GLI1 to modulate salivary acinar differentiation and 
      to promote proliferation of ductal epithelial cells.
CI  - Copyright (c) 2011 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Fiaschi, Marie
AU  - Fiaschi M
AD  - Center for Biosciences, Department of Biosciences and Nutrition, Karolinska 
      Institutet, Huddinge, Sweden.
FAU - Kolterud, Asa
AU  - Kolterud A
FAU - Nilsson, Mats
AU  - Nilsson M
FAU - Toftgard, Rune
AU  - Toftgard R
FAU - Rozell, Bjorn
AU  - Rozell B
LA  - eng
GR  - P01 AR047898/AR/NIAMS NIH HHS/United States
GR  - U01 CA105491/CA/NCI NIH HHS/United States
GR  - AR47898/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110918
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Gli1 protein, mouse)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
SB  - IM
MH  - Acinar Cells/pathology
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Cell Proliferation
MH  - Epithelial Cells/metabolism
MH  - Female
MH  - Hedgehog Proteins/*metabolism
MH  - Hyperplasia/metabolism/pathology
MH  - Kruppel-Like Transcription Factors/*metabolism/physiology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Salivary Glands/*metabolism/pathology
MH  - Signal Transduction/physiology
MH  - Zinc Finger Protein GLI1
PMC - PMC3204096
EDAT- 2011/09/22 06:00
MHDA- 2012/01/25 06:00
PMCR- 2012/11/01
CRDT- 2011/09/22 06:00
PHST- 2011/04/08 00:00 [received]
PHST- 2011/07/01 00:00 [revised]
PHST- 2011/07/19 00:00 [accepted]
PHST- 2011/09/22 06:00 [entrez]
PHST- 2011/09/22 06:00 [pubmed]
PHST- 2012/01/25 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - S0002-9440(11)00755-3 [pii]
AID - 10.1016/j.ajpath.2011.07.033 [doi]
PST - ppublish
SO  - Am J Pathol. 2011 Nov;179(5):2569-79. doi: 10.1016/j.ajpath.2011.07.033. Epub 
      2011 Sep 18.