Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells

Jane J. Yu, Victoria A. Robb, Tasha A. Morrison, Eric A. Ariazi, Magdalena Karbowniczek, Aristotelis Astreinidis, Chunrong Wang, Lisa Hernandez-Cuebas, Laura F. Seeholzer, Emmanuelle Nicolas, Harvey Hensley, V. Craig Jordan, Cheryl L. Walker, Elizabeth P. Henske

Research output: Contribution to journalArticle

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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 (E 2) 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. E 2-induced metastasis is associated with activation of p42/44 MARK and is completely inhibited by treatment with the MEK1/2 inhibitor, CI-1040. In vitro, E 2 inhibits anoikis of tuberin-null cells. Finally, using a bioluminescence approach, we found that E 2 enhances the survival and lung colonization of intravenously injected tuberin-null cells by 3-fold, which is blocked by treatment with CI-1040. Taken together these results reveal a new model for LAM pathogenesis in which activation of MEK-dependent pathways by E 2 leads to pulmonary metastasis via enhanced survival of detached tuberin-null cells.

Original languageEnglish (US)
Pages (from-to)2635-2640
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number8
DOIs
StatePublished - Feb 24 2009
Externally publishedYes

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Null Lymphocytes
Lymphangioleiomyomatosis
Estrogens
Neoplasm Metastasis
Lung
Survival
Anoikis
Circulating Neoplastic Cells
Mitogen-Activated Protein Kinase Kinases
Heterografts
Estradiol
tuberous sclerosis complex 2 protein
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells. / Yu, Jane J.; Robb, Victoria A.; Morrison, Tasha A.; Ariazi, Eric A.; Karbowniczek, Magdalena; Astreinidis, Aristotelis; Wang, Chunrong; Hernandez-Cuebas, Lisa; Seeholzer, Laura F.; Nicolas, Emmanuelle; Hensley, Harvey; Jordan, V. Craig; Walker, Cheryl L.; Henske, Elizabeth P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 8, 24.02.2009, p. 2635-2640.

Research output: Contribution to journalArticle

Yu, JJ, Robb, VA, Morrison, TA, Ariazi, EA, Karbowniczek, M, Astreinidis, A, Wang, C, Hernandez-Cuebas, L, Seeholzer, LF, Nicolas, E, Hensley, H, Jordan, VC, Walker, CL & Henske, EP 2009, 'Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2635-2640. https://doi.org/10.1073/pnas.0810790106
Yu, Jane J. ; Robb, Victoria A. ; Morrison, Tasha A. ; Ariazi, Eric A. ; Karbowniczek, Magdalena ; Astreinidis, Aristotelis ; Wang, Chunrong ; Hernandez-Cuebas, Lisa ; Seeholzer, Laura F. ; Nicolas, Emmanuelle ; Hensley, Harvey ; Jordan, V. Craig ; Walker, Cheryl L. ; Henske, Elizabeth P. / Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 8. pp. 2635-2640.
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