| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology |
Positive Breast Cancer Cells In vitro Induces an In vivo Molecular Phenotype of Estrogen Receptor
Negative Human Breast Tumors
1 Bioinformatics Program; 2 Division of Hematology/Oncology, Department of Internal Medicine; and 3 Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan
Requests for reprints: Dorraya El-Ashry, Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical Center, 1150 West Medical Center Drive, MSRB III, Room 5220B, Ann Arbor, MI 48109-0640. Phone: 734-764-5585; Fax: 734-764-0101; E-mail: elashryd{at}umich.edu.
Breast cancer presents as either estrogen receptor
(ER
) positive or negative, with ER
+ tumors responding to antiestrogen therapy and having a better prognosis. By themselves, mRNA expression signatures of estrogen regulation in ER
+ breast cancer cells do not account for the vast molecular differences observed between ER
+ and ER
cancers. In ER
tumors, overexpression of epidermal growth factor receptor (EGFR) or c-erbB-2, leading to increased growth factor signaling, is observed such that mitogen-activated protein (MAP) kinase (MAPK) is significantly hyperactivated compared with ER
+ breast cancer. In ER
+/progesterone receptorpositive, estrogen-dependent MCF-7 breast cancer cells, we stably overexpressed EGFR or constitutively active erbB-2, Raf, or MAP/extracellular signal-regulated kinase kinase, resulting in cell lines exhibiting hyperactivation of MAPK, estrogen-independent growth, and the reversible down-regulation of ER
expression. By global mRNA profiling, we found a "MAPK signature" of
400 genes consistently up-regulated or down-regulated in each of the MAPK+ cell lines. In several independent profile data sets of human breast tumors, the in vitro MAPK signature was able to accurately distinguish ER+ from ER tumors. In addition, our in vitro mRNA profile data revealed distinct mRNA signatures specific to either erbB-2 or EGFR activation. A subset of breast tumor profiles was found to share extensive similarities with either the erbB-2-specific or the EGFR-specific signatures. Our results confirm that increased MAPK activation causes loss of ER
expression and suggest that hyperactivation of MAPK plays a role in the generation of the ER
phenotype in breast cancer. These MAPK+ cell lines are excellent models for investigating the underlying mechanisms behind the ER
phenotype. (Cancer Res 2006; 66(7): 3903-11)
This article has been cited by other articles:
![]() |
C. J. Creighton, S. Massarweh, S. Huang, A. Tsimelzon, S. G. Hilsenbeck, C. K. Osborne, J. Shou, L. Malorni, and R. Schiff Development of Resistance to Targeted Therapies Transforms the Clinically Associated Molecular Profile Subtype of Breast Tumor Xenografts Cancer Res., September 15, 2008; 68(18): 7493 - 7501. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Creighton, A. Casa, Z. Lazard, S. Huang, A. Tsimelzon, S. G. Hilsenbeck, C. K. Osborne, and A. V. Lee Insulin-Like Growth Factor-I Activates Gene Transcription Programs Strongly Associated With Poor Breast Cancer Prognosis J. Clin. Oncol., September 1, 2008; 26(25): 4078 - 4085. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Eralp, D. Derin, Y. Ozluk, E. Yavuz, N. Guney, P. Saip, M. Muslumanoglu, A. Igci, S. Kucucuk, M. Dincer, et al. MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer Ann. Onc., April 1, 2008; 19(4): 669 - 674. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Massarweh, C. K. Osborne, C. J. Creighton, L. Qin, A. Tsimelzon, S. Huang, H. Weiss, M. Rimawi, and R. Schiff Tamoxifen Resistance in Breast Tumors Is Driven by Growth Factor Receptor Signaling with Repression of Classic Estrogen Receptor Genomic Function Cancer Res., February 1, 2008; 68(3): 826 - 833. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Lopez-Tarruella and R. Schiff The Dynamics of Estrogen Receptor Status in Breast Cancer: Re-shaping the Paradigm Clin. Cancer Res., December 1, 2007; 13(23): 6921 - 6925. [Full Text] [PDF] |
||||
![]() |
J. Bayliss, A. Hilger, P. Vishnu, K. Diehl, and D. El-Ashry Reversal of the Estrogen Receptor Negative Phenotype in Breast Cancer and Restoration of Antiestrogen Response Clin. Cancer Res., December 1, 2007; 13(23): 7029 - 7036. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Fiskus, Y. Ren, A. Mohapatra, P. Bali, A. Mandawat, R. Rao, B. Herger, Y. Yang, P. Atadja, J. Wu, et al. Hydroxamic Acid Analogue Histone Deacetylase Inhibitors Attenuate Estrogen Receptor-{alpha} Levels and Transcriptional Activity: A Result of Hyperacetylation and Inhibition of Chaperone Function of Heat Shock Protein 90 Clin. Cancer Res., August 15, 2007; 13(16): 4882 - 4890. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Massarweh and R. Schiff Unraveling the Mechanisms of Endocrine Resistance in Breast Cancer: New Therapeutic Opportunities Clin. Cancer Res., April 1, 2007; 13(7): 1950 - 1954. [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 |