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Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 2/24/2009, Vol. 106 Issue 8, p2635-2640. 6p. 6 Graphs. - Publication Year :
- 2009
-
Abstract
- Lymphangioleiomyomatosis (LAM) is an often fatal disease primarily affecting young women in which tuberin (TSC2)-null cells metastasize to the lungs. The mechanisms underlying the striking female predominance of LAM are unknown. We report here that 17-β-estradiol (E2) causes a 3- to 5-fold increase in pulmonary metastases in male and female mice, respectively, and a striking increase in circulating tumor cells in mice bearing tuberin-null xenograft tumors. E2-induced metastasis is associated with activation of p42/44 MAPK and is completely inhibited by treatment with the MEK1/2 inhibitor, Cl-1040. In vitro, E2 inhibits anoikis of tuberin-null cells. Finally, using a bioluminescence approach, we found that E2 enhances the survival and lung colonization of intravenously injected tuberin-null cells by 3-fold, which is blocked by treatment with Cl-1040. Taken together these results reveal a new model for LAM pathogenesis in which activation of MEK-dependent pathways by E2 leads to pulmonary metastasis via enhanced survival of detached tuberin-null cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ESTROGEN
*STEROID hormones
*METASTASIS
*CANCER invasiveness
*CARCINOGENESIS
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 37006658
- Full Text :
- https://doi.org/10.1073/pnas.0810790106