Findings from F. Rojo and co-researchers advance knowledge in breast cancer
2009 JUL 9 - (NewsRx.com) -- According to recent research published in the journal Clinical Cancer Research, "Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) dephosphorylates mitogen-activated protein kinase [extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38], mediates breast cancer chemoresistance, and is repressible by doxorubicin in breast cancer cells. We aimed to characterize doxorubicin effects on MKP-1 and phospho-MAPKs in human breast cancers and to further study the clinical relevance of MKP-1 expression in this disease." "Doxorubicin effects on MKP-1, phospho-ERK1/2 (p-ERK1/2), phospho-JNK (p-JNK), and phospho-p38 were assayed in a panel of human breast cancer cells by Western blot and in human breast cancer were assayed ex vivo by immunohistochemistry (n = 50). MKP-1 expression was also assayed in a range of normal to malignant breast lesions (n = 30) and in a series of patients (n = 96) with breast cancer and clinical follow-up. MKP-1 was expressed at low levels in normal breast and in usual ductal hyperplasia and at high levels in in situ carcinoma. MKP-1 was overexpressed in similar to 50% of infiltrating breast carcinomas. Similar to what was observed in breast cancer cell lines, ex vivo exposure of breast tumors to doxorubicin down-regulated MKP-1, and up-regulated p-ERK1/2 and p-JNK, in the majority of cases. However, in a proportion of tumors overexpressing MKP-1, doxorubicin did not significantly affect MKP-1 or phospho-MAPKs. With regard to patient outcome, MKP-1 overexpression was an adverse prognostic factor for relapse both by univariate (P < 0.001) and multivariate analysis (P = 0.002). MKP-1 is overexpressed during the malignant transformation of the breast and independently predicts poor prognosis," wrote F. Rojo and colleagues. The researchers concluded: "Furthermore, MKP-1 is repressed by doxorubicin in many human breast cancers." Rojo and colleagues published their study in Clinical Cancer Research (Mitogen-Activated Protein Kinase Phosphatase-1 in Human Breast Cancer Independently Predicts Prognosis and Is Repressed by Doxorubicin. Clinical Cancer Research, 2009;15(10):3530-3539). For additional information, contact J. Albanell, Hospital del Mar, Medical Oncology Service, IMAS, Passeig Maritim 25-29, Barcelona 08003, Spain. The publisher's contact information for the journal Clinical Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA. Keywords: Spain, Barcelona, Breast Cancer, Breast Carcinoma, Cancer Research, Doxorubicin Hydrochloride, Drug Resistance, Drugs, Enzyme Research, Experimental Design, Kinase, Oncology, Pharmaceuticals, Phosphatase, Therapy, Treatment, Women's Health. This article was prepared by Women's Health Weekly editors from staff and other reports. Copyright 2009, Women's Health Weekly via NewsRx.com.
|
