Interferon-gamma-Jak-Stat signaling in pulmonary lymphangioleiomyomatosis and renal angiomyolipoma: a potential therapeutic target

Am J Respir Cell Mol Biol. 2005 Sep;33(3):227-30. doi: 10.1165/rcmb.2005-0152RC. Epub 2005 Jun 30.

Abstract

Pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML) are proliferative lesions that occur in sporadic patients, and at much higher frequency in patients with tuberous sclerosis (TSC). The TSC1 and TSC2 genes play a critical role in their pathogenesis. Here we report a marked decrease in interferon (IFN)-gamma expression in both sporadic and TSC-associated AML and LAM. A marked increase in Stat1 expression and phosphorylation at Ser 727, and in phospho-Tyr705-Stat3 levels, was also seen in both AML and LAM tissues. Our results demonstrate that the IFN-gamma-Jak-Stat pathway is perturbed in TSC-related and sporadic LAM and AML, and suggest that IFN-gamma has potential therapeutic benefit for treatment of those lesions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiomyolipoma / metabolism*
  • Angiomyolipoma / therapy
  • Animals
  • DNA-Binding Proteins / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Janus Kinase 1
  • Janus Kinase 2
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / therapy
  • Lymphangioleiomyomatosis / metabolism*
  • Lymphangioleiomyomatosis / therapy
  • Mice
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins / physiology
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Signal Transduction / physiology*
  • Trans-Activators / metabolism
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / physiology

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • TSC1 protein, human
  • TSC2 protein, human
  • Trans-Activators
  • Tsc1 protein, mouse
  • Tsc2 protein, mouse
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • JAK2 protein, human
  • Jak1 protein, mouse
  • Jak2 protein, mouse
  • Janus Kinase 1
  • Janus Kinase 2