American Association for Cancer Research
Browse
15357163mct150920-sup-158288_2_supp_3604824_yb2h9v.docx (2.16 MB)

Supplementary Figures S1-S3 and Tables S1-S4 from c-Jun N-Terminal Kinase Inactivation by Mitogen-Activated Protein Kinase Phosphatase 1 Determines Resistance to Taxanes and Anthracyclines in Breast Cancer

Download (2.16 MB)
journal contribution
posted on 2023-04-03, 15:22 authored by Raúl Rincón, Sandra Zazo, Cristina Chamizo, Rebeca Manso, Paula González-Alonso, Ester Martín-Aparicio, Ion Cristóbal, Carmen Cañadas, Rosario Perona, Ana Lluch, Pilar Eroles, Jesús García-Foncillas, Joan Albanell, Ana Rovira, Juan Madoz-Gúrpide, Federico Rojo

Supplementary Figure S1. MKP-1 protein abundance levels in MDA-MB-231 cells treated with docetaxel at progressively increasing times. Supplementary Figure S2. Cell growth in the presence of the docetaxel or doxorubicin of breast cancer cell lines overexpressing MKP-1. Supplementary Table S1. Clinical and molecular characteristics of a series of 350 patients with early breast cancer. Supplementary Figure S3. IHC detection of MKP-1 and p-JNK1/2 in a representative normal tissue sample. Supplementary Table S2. Univariate and multivariate Cox analyses in the cohort of 350 breast cancer patients (disease-free survival analysis). Supplementary Table S3. Clinical and molecular characteristics of 64 locally advanced breast cancer patients who received neoadjuvant taxane-based chemotherapy.Supplementary Table S4. MKP-1 and p-JNK1/2 marker determinations in locally advanced breast cancer patients who received neoadjuvant taxane-based chemotherapy.

Funding

Spanish Ministry of Economy and Competitiveness

Ministry of Health

Community of Madrid

Government of Catalonia

MINECO

Institute of Health Carlos III

RETICS Biobanks Network

Fundación Jimínez Díaz Biobank

Parc de Salut Mar Biobank

Valencia Clinic Hospital Biobank

Biobanks initiative

intensification program ISCIII/FEDER

Fundación Conchita Rábago de Jiménez Díaz grants

History

ARTICLE ABSTRACT

MAPK phosphatase-1 (MKP-1) is overexpressed during malignant transformation of the breast in many patients, and it is usually associated with chemoresistance through interference with JNK-driven apoptotic pathways. Although the molecular settings of the mechanism have been documented, details about the contribution of MKP-1 to the failure of chemotherapeutic interventions are unclear. Transient overexpression of MKP-1 and treatment with JNK-modulating agents in breast carcinoma cells confirmed the mediation of MKP-1 in the resistance to taxanes and anthracyclines in breast cancer, through the inactivation of JNK1/2. We next assessed MKP-1 expression and JNK1/2 phosphorylation status in a large cohort of samples from 350 early breast cancer patients treated with adjuvant anthracycline–based chemotherapy. We detected that MKP-1 overexpression is a recurrent event predominantly linked to dephosphorylation of JNK1/2 with an adverse impact on relapse of the tumor and overall and disease-free survival. Moreover, MKP-1 and p-JNK1/2 determinations in 64 locally advanced breast cancer patients treated with neoadjuvant taxane–based chemotherapy showed an inverse correlation between MKP-1 overexpression (together with JNK1/2 inhibition) and the pathologic response of the tumors. Our results emphasize the importance of MKP-1 as a potential predictive biomarker for a subset of breast cancer patients with worse outcome and less susceptibility to treatment. Mol Cancer Ther; 15(11); 2780–90. ©2016 AACR.