Identification of the benign mesenchymal tumor gene HMGA2 in lymphangiomyomatosis

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Show simple item record D'Armiento, J Imai, K Schiltz, J Kolesnekova, N Sternberg, D Benson, K Selman, M Smolarek, T Vundavalli, M Sonnet, J Szabolcs, M Chada, K Pardo-Cemo, Annie 2011-01-22T10:26:20Z 2011-01-22T10:26:20Z 2007
dc.identifier.issn 85472
dc.description.abstract The normal expression pattern of HMGA2, an architectural transcription factor, is primarily restricted to cells of the developing mesenchyme before their overt differentiation during organogenesis. A detailed in situ hybridization analysis showed that the undifferentiated mesoderm of the embryonic lung expressed Hmga2 but it was not expressed in the newborn or adult lung. Previously, HMGA2 was shown to be misexpressed in a number of benign, differentiated mesenchymal tumors including lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. Here, we show that HMGA2 is misexpressed in pulmonary lymphangiomyomatosis (LAM), a severe disorder of unknown etiology consisting of lymphatic smooth muscle cell proliferation that results in the obstruction of airways, lymphatics, and vessels. Immunohistochemistry was done with antibodies to HMGA2 and revealed expression in lung tissue samples obtained from 21 patients with LAM. In contrast, HMGA2 was not expressed in sections of normal adult lung or other proliferative interstitial lung diseases, indicating that the expression of HMGA2 in LAM represents aberrant gene activation and is not due solely to an increase in cellular proliferation. In vivo studies in transgenic mice show that misexpression of HMGA2 in smooth muscle cells resulted in increased proliferation of these cells in the lung surrounding the epithelial cells. Therefore, similar to the other mesenchymal neoplasms, HMGA2 misexpression in the smooth muscle cell leads to abnormal proliferation and LAM tumorigenesis. These results suggest that HMGA2 plays a central role in the pathogenesis of LAM and is a potential candidate as a therapeutic target. en_US
dc.language.iso en en_US
dc.title Identification of the benign mesenchymal tumor gene HMGA2 in lymphangiomyomatosis
dc.type Artículo de investigación en_US
dc.identifier.idprometeo 1240
dc.identifier.doi 10.1158/0008-5472.CAN-06-1122
dc.source.novolpages 67(5):1902-1909
dc.subject.wos Oncology
dc.description.index WoS: SCI, SSCI o AHCI
dc.relation.journal Cancer Research
dc.description.Departamento Departamento de Biología Comparada

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