Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression.
OBJECTIVE
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.


METHODS
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 (chi(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.
Adeyinka
Adewale
A
Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba, R3E 0W3 Canada.
Nui
Yulian
Y
Cherlet
Tracy
T
Snell
Linda
L
Watson
Peter H
PH
Murphy
Leigh C
LC
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016612:Paraffin Embedding; D013629:Tamoxifen / Q000627:therapeutic use*
D013629:Tamoxifen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases