Interferon-gamma-Jak-Stat signaling in pulmonary lymphangioleiomyomatosis and renal angiomyolipoma: a potential therapeutic target.
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.
El-Hashemite
Nisreen
N
Brigham and Women's Hospital, Hematology Division, Department of Medicine, Harvard Medical School, 75 Francis Street, Boston MA 02115, USA.
Kwiatkowski
David J
DJ
D018207:Angiomyolipoma / Q000378:metabolism* / Q000628:therapy; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000628:therapy; D008175:Lung Neoplasms / Q000378:metabolism* / Q000628:therapy; D018192:Lymphangioleiomyomatosis / Q000378:metabolism* / Q000628:therapy; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000502:physiology
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D015534:Trans-Activators; C000624651:Tsc1 protein, mouse; C000624654:Tsc2 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507905:Jak1 protein, mouse; C507926:Jak2 protein, mouse; D053613:Janus Kinase 1; D053614:Janus Kinase 2