title: Elevated expression of phosphorylated c-Jun NH2-terminal kinase in basal-like and "triple-negative" breast cancers.
abstract: Basal-like carcinomas and human epidermal growth factor receptor 2 (HER-2/neu) overexpression carcinomas are the subgroups of breast cancers that have the most aggressive clinical behavior. Phosphorylation/activation of c-Jun NH2-terminal kinase is characterized as a stress-activated protein kinase, which regulates apoptosis after cellular stress. The aim of this study was to evaluate the association of phosphorylated c-Jun NH2-terminal kinase expression with phenotypes and clinicopathologic parameters of breast cancer. Phosphorylated c-Jun NH2-terminal kinase was immunohistochemically measured in a cohort of 160 patients with invasive breast cancer treated with therapeutic surgery followed by anthracycline or docetaxel-based chemotherapy. These results were further correlated with the phenotypes and clinicopathologic characteristics of breast cancers. Increased phosphorylated c-Jun NH2-terminal kinase expression was significantly associated with lack of estrogen receptor expression (P < .0001), positivity for cytokeratins 5/6 (P = .029), epidermal growth factor receptor (P = .035), basal-like phenotype (P = .015), and "triple-negative" phenotype (P = .01). Furthermore, the positive expression of phosphorylated c-Jun NH2-terminal kinase was positively correlated with p-glycoprotein (r = 0.54, P < .0001) and multidrug resistance-associated protein 1(r = 0.38, P < .0001) but not with lung resistance protein (r = -0.02, P = .78). Our results indicate that the activation of phosphorylated c-Jun NH2-terminal kinase may play a role in the carcinogenesis of basal-like and triple-negative breast carcinoma.
authors.affiliation: Department of Breast Surgery, Jinan Central Hospital, Shandong University School of Medicine, Jinan 250013, China. wangxiao@sdu.edu.cn
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Chao
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Guohui
authors.initials: G
authors.lastname: Ma
authors.forename: Liansheng
authors.initials: L
authors.lastname: Chen
authors.forename: Yixiu
authors.initials: Y
authors.lastname: Zang
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000601:surgery; D001943:Breast Neoplasms / Q000378:metabolism* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000601:surgery; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000601:surgery; D018276:Carcinoma, Medullary / Q000378:metabolism* / Q000601:surgery; D016009:Chi-Square Distribution; D004815:Epidermal Growth Factor / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D018579:Patient Selection; D010766:Phosphorylation; D015854:Up-Regulation; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004815:Epidermal Growth Factor; D047628:Estrogen Receptor alpha; D048031:JNK Mitogen-Activated Protein Kinases; D007633:Keratins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein