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| Status |
Public on Oct 21, 2009 |
| Title |
Rapamycin-insensitive up-regulation of MMP2 and other genes in TSC2- deficient LAM-like cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Rationale:
Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of lymphangioleiomyomatosis (LAM).
Objectives:
To investigate how TSC1 or TSC2 deficiency alters MMP expression and regulation.
Methods:
We studied immortalized cells that lack TSC2 derived from an angiomyolipoma (AML) of a LAM patient, and a TSC2 add back derivative; and murine embryonic fibroblast cells that lack Tsc1 or Tsc2 and respective controls. Global gene expression analysis was carried out in the AML and derivative cell lines. MMP levels in the conditioned media from these cells were analyzed by zymography and ELISA.
Measurements and Main Results:
We found increased MMP-2 expression in cells lacking TSC1/TSC2 compared to 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 over-expressed in rapamycin-treated TSC2-deficient cells compared to TSC2+ cells.
Conclusions:
We conclude that TSC1/TSC2 deficiency leads to MMP-2 overproduction that is rapamycin insensitive, and that several genes exhibit similar patterns suggesting TSC1/TSC2 dependent but mTOR independent pathways may be involved in the pathogenesis of LAM.
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| Overall design |
We studied immortalized cells that lack TSC2 derived from an angiomyolipoma (AML) of a LAM patient, and a TSC2 add back derivative. Global gene expression analysis was carried out in the AML and derivative cell lines. MMP levels in the conditioned media from these cells were analyzed by zymography and ELISA.
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| Contributor(s) |
Lee P, Tsang SW, Moses MA, Trayes-Gibson Z, Hsiao L, Jensen R, Squillace R, Kwiatkowski DJ |
| Citation(s) |
19395678 |
| Submission date |
Jul 02, 2009 |
| Last update date |
Oct 28, 2014 |
| Contact name |
Po-Shun Lee |
| E-mail(s) |
plee@rics.bwh.harvard.edu
|
| Phone |
617-355-9012
|
| Fax |
617-355-9016
|
| Organization name |
Brigham & Women's Hospital
|
| Department |
Medicine
|
| Street address |
1 Blackfan Circle, Karp 6
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL2895 |
GE Healthcare/Amersham Biosciences CodeLink Human Whole Genome Bioarray |
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| Samples (9)
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| GSM424642 |
cultured cells TSC2-/- treated with rapamycin rep1 |
| GSM426549 |
cultured cells TSC2-/- treated with rapamycin rep2 |
| GSM426550 |
cultured cells TSC2-/- treated with rapamycin rep3 |
|
| Relations |
| BioProject |
PRJNA117303 |
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