title: Molecular Profiling and Malignant Behavior Define Two Rat Mammary Tumor Cell Lines as a Relevant Experimental Model.
abstract: Cancer cell lines have become a reliable tool in genetic and biochemical studies of breast cancer. Here, we described the behavior and novel molecular characterization of two cell lines derived from DMBA-induced rat mammary tumor, LA7 and RBA. LA7 cells have been identified as myoepithelial cells with stem cell properties, whereas the RBA cell line are epithelial cells that present mutational activated H-Ras, but are much less known. We evaluated the proliferation rate and molecular markers, several signaling pathways status related to proliferation, survival, inflammation, and apoptosis, as well as migration capacity, global DNA methylation levels, and stem cells populations. In fact, we found the A/T transversion in the c-Ha-Ras codon 61 as the activator mutation origin described in RBA cells. LA7 and RBA cells showed a high proliferation rate associated with overexpression of Cyclin D1, and resistance to apoptotic signals due to lack of expression of Bad. Moreover, neither of these two cell lines expressed steroid receptors, but they showed high migration capacity, all in accordance with an aggressive phenotype. We found global DNA methylation levels in LA7 and RBA cells lower than reference tissues analyzed, in addition to the presence of different stem cells populations in RBA cell line that differed in the expression of CD44 and CD24. These results revealed a malignant behavior associated with cancer stem cell phenotype. Since this profile is similar to a human triple-negative basal-like tumor, their extensive characterization presented herein increases their value as a good in vitro model. J. Cell. Biochem. 117: 2825-2834, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Physiology Unit, Faculty of Medicine, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Vela
authors.affiliation: Physiology Unit, Faculty of Medicine, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain. eduard.escrich@uab.es.
authors.forename: Eduard
authors.initials: E
authors.lastname: Escrich
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019175:DNA Methylation; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D051381:Rats
chemical_list: D014408:Biomarkers, Tumor
keywords: BREAST CANCER; DMBA; LA7; RAT; RBA