Journal of Surgical Research
Volume 138, Issue 1 , Pages 37-44 , March 2007

Rapamycin Inhibits Proliferation of Estrogen-Receptor-Positive Breast Cancer Cells

Presented at the 1st Annual Academic Surgical Congress (Association for Academic Surgery), San Diego, CA, February 7–11, 2006.

  • Sharon B. Chang, M.D.

      Affiliations

    • Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts
    • Department of Surgery, University of California, Davis Medical Center, Sacramento, California
    • Department of Surgery, Brigham and Women’s Hospital, Boston, Massachusetts
    • Corresponding Author InformationTo whom correspondence and reprint requests should be addressed at Department of Surgery, University of California, Davis Medical Center, 2315 Stockton Blvd. #6309, Sacramento, CA 95817.
  • ,
  • Penelope Miron, Ph.D.

      Affiliations

    • Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • ,
  • Alexander Miron, Ph.D.

      Affiliations

    • Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • ,
  • J. Dirk Iglehart, M.D.

      Affiliations

    • Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts
    • Department of Surgery, Brigham and Women’s Hospital, Boston, Massachusetts

Received 11 June 2006

References 

  1. Sehgal SN. Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003;35:7S
  2. Ponticelli C. The pleiotropic effects of mTor inhibitors. J Nephrol. 2004;17:762
  3. van der Hoeven BL, Pires NM, Warda HM, et al. Drug-eluting stents: results, promises and problems. Int J Cardiol. 2005;99:9
  4. Monks A, Scudiero D, Skehan P, et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst. 1991;83:757
  5. Dancey JE. Clinical development of mammalian target of rapamycin inhibitors. Hematol Oncol Clin North Am. 2002;16:1101
  6. Jacinto E, Hall MN. Tor signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol. 2003;4:117
  7. Hidalgo M, Rowinsky EK. The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene. 2000;19:6680
  8. Inoki K, Ouyang H, Li Y, et al. Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev. 2005;69:79
  9. 2005 Cancer Facts and Figures. American Cancer Society.
  10. Johnston SR, Dowsett M, Smith IE. Towards a molecular basis for tamoxifen resistance in breast cancer. Ann Oncol. 1992;3:503
  11. Yu K, Toral-Barza L, Discafani C, et al. mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer. 2001;8:249
  12. Simoncini T, Hafezi-Moghadam A, Brazil DP, et al. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature. 2000;407:538
  13. Sun M, Paciga JE, Feldman RI, et al. Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res. 2001;61:5985
  14. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27
  15. Bjornstrom L, Sjoberg M. Mechanisms of estrogen receptor signaling: convergence of genomic and non-genomic actions on target genes. Mol Endocrinol. 2005;19:833
  16. Stoica GE, Franke TF, Wellstein A, et al. Estradiol rapidly activates Akt via the ErbB2 signaling pathway. Mol Endocrinol. 2003;17:818
  17. Majumder PK, Febbo PG, Bikoff R, et al. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med. 2004;10:594
  18. Noh WC, Mondesire WH, Peng J, et al. Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res. 2004;10:1013
  19. Podsypanina K, Lee RT, Politis C, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/− mice. Proc Natl Acad Sci USA. 2001;98:10320
  20. Lobenhofer EK, Marks JR. Estrogen-induced mitogenesis of MCF-7 cells does not require the induction of mitogen-activated protein kinase activity. J Steroid Biochem Mol Biol. 2000;75:11
  21. deGraffenried LA, Friedrichs WE, Russell DH, et al. Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity. Clin Cancer Res. 2004;10:8059
  22. Huang S, Bjornsti MA, Houghton PJ. Rapamycins: mechanism of action and cellular resistance. Cancer Biol Ther. 2003;2:222
  23. Clemons M, Danson S, Howell A. Tamoxifen (“Nolvadex”): a review. Cancer Treat Rev. 2002;28:165
  24. Awada A, Cardosa F, Fontaine C, et al. A phase Ib study of the mTOR inhibitor RAD001 (everolimus) in combination with letrozole (Femara), investigating safety and pharmacokinetics in patients with advanced breast cancer stable or slowly progressing on letrozole [Abstract]. Breast Cancer Res Treat. 2004;88:S234

PII: S0022-4804(06)00358-1

doi: 10.1016/j.jss.2006.07.003

Journal of Surgical Research
Volume 138, Issue 1 , Pages 37-44 , March 2007