To evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients.
Thus, the patterns of localization and expression of components of the IGF system in LAM strongly suggest that these agents are involved in the proliferation of LAM cells.
These data demonstrate that tuberin negatively regulates the activity of S6 and p70S6K specifically, and suggest a potential mechanism for abnormal cell growth in LAM.
A calmodulin binding site in the tuberous sclerosis 2 gene product is essential for regulation of transcription events and is altered by mutations linked to tuberous sclerosis and lymphangioleiomyomatosis.
Focal cortical dysplasia of Taylor's balloon cell type: mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis.
However, our study indicates that a fraction of sporadic LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even for patients with sporadic LAM.
However, our study indicates that a fraction of sporadic LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even for patients with sporadic LAM.
However, our study indicates that a fraction of sporadic LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even for patients with sporadic LAM.
Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM).
These data demonstrate that tuberin negatively regulates the activity of S6 and p70S6K specifically, and suggest a potential mechanism for abnormal cell growth in LAM.
Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM).
We used microsatellite marker fingerprinting and TSC2 gene mutational analysis to study a patient with recurrent LAM after single-lung transplantation.
Tissue inhibitor of metalloproteinase-3 downregulation in lymphangioleiomyomatosis: potential consequence of abnormal serum response factor expression.
Because timp-3-null mice develop spontaneous emphysema, our findings suggest that SRF-mediated TIMP-3 inhibition might contribute to the tissue damage seen in LAM.
Recent studies, however, revealed that both forms of LAM are genetically related but that sporadic LAM is a distinct clinical entity caused by somatic mutations of TSC2 (not TSC1) rather than a forme fruste of TSC carrying either of the TSC1 or TSC2 germline mutations.
Recent studies, however, revealed that both forms of LAM are genetically related but that sporadic LAM is a distinct clinical entity caused by somatic mutations of TSC2 (not TSC1) rather than a forme fruste of TSC carrying either of the TSC1 or TSC2 germline mutations.
Using laser microdissection, we extend our studies to the analysis of SMCs from LAM nodules where we observe higher MMP1 expression and MMP2 activation.
To test the hypothesis that DDR may be involved in ECM remodeling by SMCs in vivo, we analyzed DDR expression by reverse transcriptase-polymerase chain reaction and immunohistochemistry and demonstrate that both DDR1 and DDR2 are up-regulated in nodules of LAM as compared to normal controls, and are expressed in lesions of atherosclerosis.