| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics, Molecular Targets, and Chemical Biology |
1 Program in Signal Transduction Research, 2 Oncodevelopmental Biology Program, and 3 Developmental Neurobiology Program, The Burnham Institute, La Jolla, California
Requests for reprints: Robert T. Abraham, Program in Signal Transduction Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037. Phone: 858-646-3182; Fax: 858-713-6268; E-mail: abraham{at}burnham.org.
The ErbB2 (Neu) receptor tyrosine kinase is frequently overexpressed in human breast cancers, and this phenotype correlates with a poor clinical prognosis. We examined the effects of the mammalian target of rapamycin inhibitor, rapamycin, on mammary tumorigenesis in transgenic mice bearing an activated ErbB2 (NeuYD) transgene in the absence or presence of a second transgene encoding vascular endothelial growth factor (VEGF). Treatment of NeuYD or NeuYD x VEGF mice with rapamycin dramatically inhibited tumor growth accompanied by a marked decrease in tumor vascularization. Two key events that may underlie the antitumor activity of rapamycin were decreased expression of ErbB3 and inhibition of hypoxia-inducible factor-1–dependent responses to hypoxic stress. Rapamycin exposure caused only a modest inhibition of the proliferation of tumor-derived cell lines in standard monolayer cultures, but dramatically inhibited the growth of the same cells in three-dimensional cultures, due in part to the induction of apoptotic cell death. These studies underscore the therapeutic potential of mammalian target of rapamycin inhibitors in ErbB2-positive breast cancers and indicate that, relative to monolayer cultures, three-dimensional cell cultures are more predictive in vitro models for studies of the antitumor mechanisms of rapamycin and related compounds.
This article has been cited by other articles:
|
|
 |
|
  P. A. Dennis Rapamycin for Chemoprevention of Upper Aerodigestive Tract Cancers Cancer Prevention Research, January 1, 2009; 2(1): 7 - 9. [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Wilson, D. Barbone, T.-M. Yang, D. M. Jablons, R. Bueno, D. J. Sugarbaker, S. L. Nishimura, G. J. Gordon, and V. C. Broaddus mTOR Mediates Survival Signals in Malignant Mesothelioma Grown as Tumor Fragment Spheroids Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 576 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Barbone, T.-M. Yang, J. R. Morgan, G. Gaudino, and V. C. Broaddus Mammalian Target of Rapamycin Contributes to the Acquired Apoptotic Resistance of Human Mesothelioma Multicellular Spheroids J. Biol. Chem., May 9, 2008; 283(19): 13021 - 13030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ramos-Barron, C. Pinera-Haces, C. Gomez-Alamillo, I. Santiuste-Torcida, J.C. Ruiz, L. Buelta-Carrillo, R. Merino, A.L.M. de Francisco, and M. Arias Prevention of murine lupus disease in (NZBxNZW)F1 mice by sirolimus treatment Lupus, October 1, 2007; 16(10): 775 - 781. [Abstract] [PDF]
|
|
|
|
 |
|
 A. L. Howes, G. G. Chiang, E. S. Lang, C. B. Ho, G. Powis, K. Vuori, and R. T. Abraham The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures Mol. Cancer Ther., September 1, 2007; 6(9): 2505 - 2514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Mosley, J. T. Poirier, D. D. Seachrist, M. D. Landis, and R. A. Keri Rapamycin inhibits multiple stages of c-Neu/ErbB2 induced tumor progression in a transgenic mouse model of HER2-positive breast cancer Mol. Cancer Ther., August 1, 2007; 6(8): 2188 - 2197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Kopelovich, J. R. Fay, C. C. Sigman, and J. A. Crowell The Mammalian Target of Rapamycin Pathway as a Potential Target for Cancer Chemoprevention Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1330 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Abraham and J. J. Gibbons The Mammalian Target of Rapamycin Signaling Pathway: Twists and Turns in the Road to Cancer Therapy Clin. Cancer Res., June 1, 2007; 13(11): 3109 - 3114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Wu, K. Kiguchi, T. Kawamoto, T. Ajiki, J. Traag, S. Carbajal, L. Ruffino, H. Thames, I. Wistuba, M. Thomas, et al. Therapeutic Effect of Rapamycin on Gallbladder Cancer in a Transgenic Mouse Model Cancer Res., April 15, 2007; 67(8): 3794 - 3800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Granville, N. Warfel, J. Tsurutani, M. C. Hollander, M. Robertson, S. D. Fox, T. D. Veenstra, H. J. Issaq, R. I. Linnoila, and P. A. Dennis Identification of a Highly Effective Rapamycin Schedule that Markedly Reduces the Size, Multiplicity, and Phenotypic Progression of Tobacco Carcinogen-Induced Murine Lung Tumors Clin. Cancer Res., April 1, 2007; 13(7): 2281 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Cardiff, M. R. Anver, G. P. Boivin, M. W. Bosenberg, R. R. Maronpot, A. A. Molinolo, A. Y. Nikitin, J. E. Rehg, G. V. Thomas, R. G. Russell, et al. Precancer in Mice: Animal Models Used to Understand, Prevent, and Treat Human Precancers Toxicol Pathol, October 1, 2006; 34(6): 699 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Birle and D. W. Hedley Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma xenografts. Mol. Cancer Ther., October 1, 2006; 5(10): 2494 - 2502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Carver and P. P. Pandolfi Mouse modeling in oncologic preclinical and translational research. Clin. Cancer Res., September 15, 2006; 12(18): 5305 - 5311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Garcia-Morales, E. Hernando, E. Carrasco-Garcia, M. P. Menendez-Gutierrez, M. Saceda, and I. Martinez-Lacaci Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer cells. Mol. Cancer Ther., September 1, 2006; 5(9): 2172 - 2181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Namba, L. J.T. Young, C. K. Abbey, L. Kim, P. Damonte, A. D. Borowsky, J. Qi, C. G. Tepper, C. L. MacLeod, R. D. Cardiff, et al. Rapamycin Inhibits Growth of Premalignant and Malignant Mammary Lesions in a Mouse Model of Ductal Carcinoma In situ Clin. Cancer Res., April 15, 2006; 12(8): 2613 - 2621. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
