PMID- 18094094
OWN - NLM
STAT- MEDLINE
DCOM- 20080307
LR  - 20240322
IS  - 1546-3222 (Print)
IS  - 1546-3222 (Linking)
VI  - 5
IP  - 1
DP  - 2008 Jan 1
TI  - Smooth muscle-like cells in pulmonary lymphangioleiomyomatosis.
PG  - 119-26
AB  - Proliferation, migration, and differentiation of smooth muscle (SM)-like 
      lymphangioleiomyomatosis (LAM) cells in the lungs are pathologic manifestations 
      of pulmonary LAM, a rare lung disease predominantly afflicting women and 
      exacerbated by pregnancy. LAM cells form nodules throughout the lung without any 
      predominant localization, but can also form small cell clusters dispersed within 
      lung parenchyma. LAM cells have the appearance of "immature" SM-like cells, 
      irregularly distributed within the nodule in contrast to organized SM cell layers 
      in airways and vasculature. Progressive growth of LAM cells leads to the cystic 
      destruction of the lung parenchyma, obstruction of airways and lymphatics, and 
      loss of pulmonary function. Pathogenetically, LAM occurs from somatic or genetic 
      mutations of tumor suppressor genes tuberous sclerosis complex 1 (TSC1) or TSC2. 
      The TSC1/TSC2 protein complex is an integrator of signaling networks regulated by 
      growth factors, insulin, nutrients, and energy. The observation that the 
      TSC1/TSC2 functions as a negative regulator of the mammalian target of rapamycin 
      (mTOR)/p70 S6 kinase (S6K1) signaling pathway yielded the first rapamycin 
      clinical trial for LAM. Although LAM is a rare lung disease, the elucidation of 
      disease-relevant mechanisms of LAM will provide a better understanding of not 
      only SM-like cell growth, migration, and differentiation in LAM but may also 
      offer insights into other metabolic diseases such as cardiovascular diseases, 
      diabetes, and cancer. In this article, we will summarize the progress made in our 
      understanding of LAM, and we will focus on how dysregulation of TSC1/TSC2 
      signaling results in abnormal proliferation and migration of SM-like LAM cells.
FAU - Krymskaya, Vera P
AU  - Krymskaya VP
AD  - Pulmonary Allergy and Critical Care Division, Department of Medicine, University 
      of Pennsylvania, Philadelphia, PA 19104-3403, USA. krymskay@mail.med.upenn.edu
LA  - eng
GR  - 2R01HL071106/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Proc Am Thorac Soc
JT  - Proceedings of the American Thoracic Society
JID - 101203596
RN  - 0 (TSC1 protein, human)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Cell Proliferation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Lung Neoplasms/*pathology
MH  - Lymphangioleiomyomatosis/*pathology
MH  - Myocytes, Smooth Muscle/*pathology
MH  - Signal Transduction
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*metabolism
PMC - PMC2645298
EDAT- 2007/12/21 09:00
MHDA- 2008/03/08 09:00
PMCR- 2009/01/01
CRDT- 2007/12/21 09:00
PHST- 2007/12/21 09:00 [pubmed]
PHST- 2008/03/08 09:00 [medline]
PHST- 2007/12/21 09:00 [entrez]
PHST- 2009/01/01 00:00 [pmc-release]
AID - 5/1/119 [pii]
AID - procats51119 [pii]
AID - 10.1513/pats.200705-061VS [doi]
PST - ppublish
SO  - Proc Am Thorac Soc. 2008 Jan 1;5(1):119-26. doi: 10.1513/pats.200705-061VS.