title: The microRNA expression associated with morphogenesis of breast cancer             cells in three-dimensional organotypic culture.
abstract: Three-dimensional organotypic culture using reconstituted basement membrane matrix Matrigel (rBM 3-D) is an indispensable tool to characterize morphogenesis of mammary epithelial cells and to elucidate the tumor-modulating actions of extracellular matrix (ECM). microRNAs (miRNAs) are a novel class of oncogenes and tumor suppressors. The majority of our current knowledge of miRNA expression and function in cancer cells is derived from monolayer 2-D culture on plastic substratum, which lacks consideration of the influence of ECM-mediated morphogenesis on miRNAs. In the present study, we compared the expression of miRNAs in rBM 3-D and 2-D cultures of the non-invasive MCF-7 and the invasive MDA-MB231 cells. Our findings revealed a profound difference in miRNA profiles between 2-D and rBM 3-D cultures within each cell type. Moreover, rBM 3-D culture exhibited greater discrimination in miRNA profiles between MCF-7 and MDA-MB231 cells than 2-D culture. The disparate miRNA profiles correlated with distinct mass morphogenesis of MCF-7 and invasive stellate morphogenesis of MDA-MB231 cells in rBM 3-D culture. Supplementation of the tumor promoting type I collagen in rBM 3-D culture substantially altered the miRNA signature of mass morphologenesis of MCF-7 cells in rBM 3-D culture. Overexpression of the differentially expressed miR-200 family member miR429 in MDA-MB231 cells attenuated their invasive stellate morphogenesis in rBM 3-D culture. In summary, we provide the first miRNA signatures of morphogenesis of human breast cancer cells in rBM 3-D culture and warrant further utilization of rBM 3-D culture in investigation of miRNAs in breast cancer.
authors.affiliation: Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Hong T
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Hunan 41008.
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pathology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Pathology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Flemington
authors.affiliation: Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China.
authors.forename: Y I
authors.initials: YI
authors.lastname: Lin
authors.affiliation: Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
mesh_terms: D001943:Breast Neoplasms; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D048430:Cell Shape; D016000:Cluster Analysis; D024042:Collagen Type I / Q000502:physiology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D024042:Collagen Type I; C546363:MIRN429 microRNA, human; D035683:MicroRNAs