title: RhoC upregulation is correlated with reduced E-cadherin in human breast cancer specimens after chemotherapy and in human breast cancer MCF-7 cells.
abstract: Therapy-resistant cancer cells are a major problem in cancer research. Recent studies suggest that the epithelial-mesenchymal transition (EMT) is a key mechanism in therapy resistance. Yet, the expressions of EMT markers, EMT core regulators, and a stem cell marker of BMI1 during chemotherapy have been poorly analyzed in clinical breast cancer specimens. In the present study, we investigated the roles of RhoC under chemotherapy to follow up on earlier findings demonstrating the involvement of RhoC in prostate cancer resistance to endocrine therapy. Immunohistochemically, E-cadherin expression was significantly lower in human breast cancer specimens analyzed after chemotherapy than specimens biopsied before chemotherapy. Significant upregulation of fibronectin, a mesenchymal EMT marker, was found in post-chemotherapy analysis. A study of the EMT core regulators of SNAIL1, SNAIL2, TWIST1, and a well-known stem cell marker of BMI1 revealed no post-chemotherapy upregulation of these molecules. In contrast, RhoC expression was significantly upregulated in post-chemotherapy breast cancer specimens. MCF-7 cells stably transfected with the constitutive active (CA) RhoC plasmid manifested a reduced level of E-cadherin at the peripheries and disorganization of actin fibers, with no accompanying upregulation of SNAIL1, SNAIL2, TWIST1, or BMI1 in Western blots. Exposure of etoposide on MCF-7 cells showed RhoC upregulation together with reduced membranous expression of E-cadherin and disorganization of actin fibers. In MTT assay, however, the CA-RhoC-expressing MCF-7 cells failed to show chemotherapy resistance under etoposide treatment. Taken in sum, RhoC may contribute to an EMT-like process in human breast cancer during chemotherapy.
authors.affiliation: Department of Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kawata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kamiakito
authors.forename: Yawara
authors.initials: Y
authors.lastname: Omoto
authors.forename: Chieko
authors.initials: C
authors.lastname: Miyazaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hozumi
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D009367:Neoplasm Staging; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D015820:Cadherins; D005353:Fibronectins; D005047:Etoposide; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein