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We studied immortalized cells that lack TSC2 derived from an angiomyolipoma of a patient with LAM, a TSC2 addback derivative, and murine embryonic fibroblast cells that lack Tsc1 or -2 and respective controls. Global gene expression analysis was performed in the angiomyolipoma and derivative cell lines. MMP levels in the conditioned media from these cells were analyzed by zymography and ELISA. We found increased MMP-2 expression in cells lacking TSC1\/TSC2 compared with their respective controls by zymography. MMP-2 overproduction by these cells was not affected by rapamycin treatment. Gene expression analysis confirmed increased MMP-2 gene expression that was not affected by rapamycin. Furthermore, multiple other genes were found to be overexpressed in rapamycin-treated TSC2-deficient cells compared with TSC2+ cells. We conclude that TSC1\/TSC2 deficiency leads to MMP-2 overproduction that is rapamycin-insensitive, and that several genes exhibit similar patterns, suggesting that TSC1\/TSC2\u2013dependent, but mammalian target of rapamycin\u2013independent, pathways may be involved in the pathogenesis of LAM.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0050oc","type":"journal-article","created":{"date-parts":[[2009,4,24]],"date-time":"2009-04-24T21:59:57Z","timestamp":1240610397000},"page":"227-234","source":"Crossref","is-referenced-by-count":64,"title":["Rapamycin-Insensitive Up-Regulation of\n                    <i>MMP2<\/i>\n                    and Other Genes in Tuberous Sclerosis Complex 2\u2013Deficient Lymphangioleiomyomatosis-Like Cells"],"prefix":"10.1093","volume":"42","author":[{"given":"Po-Shun","family":"Lee","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Division"},{"name":"Translational Medicine Division, and"},{"name":"Harvard Medical School, Boston, Massachusetts; 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