| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
Departments of Biochemistry and Medical Genetics [Y. N., T. C., L. C. M.] and Pathology [A. A., L. S., P. H. W.], Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0W3 Canada
Purpose: The purpose of this study is to address the hypothesis that activatedmitogen-activated protein kinase (MAPK; extracellular signal-regulated kinases 1 and 2) has a role in breast tumorigenesis, breast cancer progression, and the development of tamoxifen resistance.
Experimental Design: H-score analysis and a specific antibody for the immunohistochemical detection of activated MAPK in formalin-fixed, paraffin-embedded tissue sections were used to compare expression in: (a) human breast tumors and their matched adjacent normal breast tissue; (b) primary human breast tumors and their matched lymph node metastases; and (c) primary breast tumors from patients who later proved to be sensitive or resistant to tamoxifen treatment.
Results: Active MAPK expression was detected in 48% of primary human breast tumors and was significantly increased in tumors compared with adjacent normal breast (Wilcoxon test, P = 0.027). A significant positive association (
2, P = 0.02; n = 55) was obtained between active MAPK and the presence of lymph node metastases. Moreover, increased active MAPK (Wilcoxon test, P = 0.0098) was found in concurrent lymph node metastases compared with primary breast tumors. No significant difference in active MAPK was found in primary tumors of patients who later responded to tamoxifen or did not respond to tamoxifen.
Conclusions: These data suggest that active MAPK is a marker of breast cancer metastasis and has a role in the metastatic process. However, active MAPK is unlikely to be a marker of endocrine sensitivity or involved in de novo tamoxifen resistance.
This article has been cited by other articles:
|
|
 |
|
  L. Ma, J. Teruya-Feldstein, P. Bonner, R. Bernardi, D. N. Franz, D. Witte, C. Cordon-Cardo, and P. P. Pandolfi Identification of S664 TSC2 Phosphorylation as a Marker for Extracellular Signal-Regulated Kinase Mediated mTOR Activation in Tuberous Sclerosis and Human Cancer Cancer Res., August 1, 2007; 67(15): 7106 - 7112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Mhaidat, X. D. Zhang, C. C. Jiang, and P. Hersey Docetaxel-Induced Apoptosis of Human Melanoma Is Mediated by Activation of c-Jun NH2-Terminal Kinase and Inhibited by the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase 1/2 Pathway Clin. Cancer Res., February 15, 2007; 13(4): 1308 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Weitsman, L. Li, G. P. Skliris, J. R. Davie, K. Ung, Y. Niu, L. Curtis-Snell, L. Tomes, P. H. Watson, and L. C. Murphy Estrogen Receptor-{alpha} Phosphorylated at Ser118 Is Present at the Promoters of Estrogen-Regulated Genes and Is Not Altered Due to HER-2 Overexpression. Cancer Res., October 15, 2006; 66(20): 10162 - 10170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Sarwar, J-S Kim, J Jiang, D Peston, H D Sinnett, P Madden, J M Gee, R I Nicholson, A E Lykkesfeldt, S Shousha, et al. Phosphorylation of ER{alpha} at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ER{alpha} phosphorylation in breast cancer progression. Endocr. Relat. Cancer, September 1, 2006; 13(3): 851 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Glaros, N. Atanaskova, C. Zhao, D. F. Skafar, and K. B. Reddy Activation Function-1 Domain of Estrogen Receptor Regulates the Agonistic and Antagonistic Actions of Tamoxifen Mol. Endocrinol., May 1, 2006; 20(5): 996 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Pandey, T. S. Udayakumar, X. Lin, D. Sharma, P. S. Shapiro, and J. D. Fondell Activation of TRAP/Mediator Subunit TRAP220/Med1 Is Regulated by Mitogen-Activated Protein Kinase-Dependent Phosphorylation Mol. Cell. Biol., December 15, 2005; 25(24): 10695 - 10710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L C Murphy, B Peng, A Lewis, J R Davie, E Leygue, A Kemp, K Ung, M Vendetti, and R Shiu Inducible upregulation of oestrogen receptor-{beta}1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells J. Mol. Endocrinol., April 1, 2005; 34(2): 553 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Murphy, Y. Niu, L. Snell, and P. Watson Phospho-Serine-118 Estrogen Receptor-{alpha} Expression Is Associated with Better Disease Outcome in Women Treated with Tamoxifen Clin. Cancer Res., September 1, 2004; 10(17): 5902 - 5906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vicent, M. Garayoa, J. M. Lopez-Picazo, M. D. Lozano, G. Toledo, F. B. J. M. Thunnissen, R. G. Manzano, and L. M. Montuenga Mitogen-Activated Protein Kinase Phosphatase-1 Is Overexpressed in Non-Small Cell Lung Cancer and Is an Independent Predictor of Outcome in Patients Clin. Cancer Res., June 1, 2004; 10(11): 3639 - 3649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Raguz, M. Tamburo De Bella, G. Tripuraneni, M. J. Slade, C. F. Higgins, R. C. Coombes, and E. Yague Activation of the MDR1 Upstream Promoter in Breast Carcinoma as a Surrogate for Metastatic Invasion Clin. Cancer Res., April 15, 2004; 10(8): 2776 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Murphy, T. Cherlet, A. Adeyinka, Y. Niu, L. Snell, and P. Watson Phospho-Serine-118 Estrogen Receptor-{alpha} Detection in Human Breast Tumors in Vivo Clin. Cancer Res., February 15, 2004; 10(4): 1354 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Izevbigie, J. L. Bryant, and A. Walker A Novel Natural Inhibitor of Extracellular Signal-Regulated Kinases and Human Breast Cancer Cell Growth Experimental Biology and Medicine, February 1, 2004; 229(2): 163 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. I. Nicholson, I. R. Hutcheson, J. M. Knowlden, H. E. Jones, M. E. Harper, N. Jordan, S. E. Hiscox, D. Barrow, and J. M. W. Gee Nonendocrine Pathways and Endocrine Resistance: Observations with Antiestrogens and Signal Transduction Inhibitors in Combination Clin. Cancer Res., January 1, 2004; 10(1): 346S - 354S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Eisenmann, M. W. VanBrocklin, N. A. Staffend, S. M. Kitchen, and H.-M. Koo Mitogen-Activated Protein Kinase Pathway-Dependent Tumor-Specific Survival Signaling in Melanoma Cells through Inactivation of the Proapoptotic Protein Bad Cancer Res., December 1, 2003; 63(23): 8330 - 8337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Jorgensen, R. Holm, G. M. Maelandsmo, and V. A. Florenes Expression of Activated Extracellular Signal-Regulated Kinases 1/2 in Malignant Melanomas: Relationship with Clinical Outcome Clin. Cancer Res., November 1, 2003; 9(14): 5325 - 5331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Handra-Luca, H. Bilal, J.-C. Bertrand, and P. Fouret Extra-Cellular Signal-Regulated ERK-1/ERK-2 Pathway Activation in Human Salivary Gland Mucoepidermoid Carcinoma: Association to Aggressive Tumor Behavior and Tumor Cell Proliferation Am. J. Pathol., September 1, 2003; 163(3): 957 - 967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zheng, P. Fiumara, Y. V. Li, G. Georgakis, V. Snell, M. Younes, J. N. Vauthey, A. Carbone, and A. Younes MEK/ERK pathway is aberrantly active in Hodgkin disease: a signaling pathway shared by CD30, CD40, and RANK that regulates cell proliferation and survival Blood, August 1, 2003; 102(3): 1019 - 1027. [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 |
