Down-Regulation of Proliferation and Cell Adhesion and Up-Regulation of Cell Migration Associated Genes in Lobular Breast Carcinomas.
Barbara Castellana, Enrique Lerma, Elena Serrano, Gloria Peiro, Dani Escuin, Ariadna Tibau, Cristina Pons, Maitane Perez, Agusti Barnadas. Hospital de la Santa Creu i Sant Pau. Universitat Autònoma, Barcelona, Spain; Hospital de Alicante, Spain
Background: The aim of this study was to identify differential gene expression between Invasive lobular carcinoma (ILC)and hormone positive inavsive ductal carcinomas (IDC).
Design: Twenty seven frozen tumor samples were selected from our tumor bank including 10 ILC and 17 IDC (10 luminal A, 7 luminal B). mRNA was isolated by standard procedure, purified and mRNA concentration and quality was checked by RNA 6000 Nano LabChip Kit (Agilent Bioanalyzer). Samples were analyzed upon Affymetrix GeneChip®Human Gene 1.0 ST Array. The expression of 8 differentially expressed genes pleckstrin homology domain containing, family A member 7 (PLEKHA7), thymosin beta 10 (TMSB10), claudin 7 (CLDN7), peroxiredoxine 4 (PRXD4),cytokeratine 5 (KRT5),metalloproteinase 2 (MMP-2),maspin (SERPINB5) and E-cadherin (CDH1) was validated by quantitative real time-PCR. CLDN7, KRT5, CDH1, MMP-2 were studied by immunohistochemistry.
Results: Compared to IDCs, ILCs displayed down-regulation of genes related to cell cycle and proliferation (AREG, ANXA2P1), cell adhesion (CASK), genes involved in TGF-beta signaling (AREG, ANXA2P1), actin cytoskeleton remodeling (TMSB10, TMSB4X), and ubiquitin proteins (UBE2L3, UBE2E3). Furthermore, ILC presented up-regulation of cell migration associated genes (FUT8, CRIPAK), ions binding and transport (GRIA2, SHROOM1, CACNA2D2), lipid/prostaglandin biosynthesis genes (PNPLA7, JMJD7-PLA2G4B) and genes related to catabolic processes (ANUBL1, CSAD). Real time PCR validated the differential expression of PLEKHA7, TMSB10, CLDN7, PRXD4, KRT5, MMP-2 and SERPINB5 (p<0.05), but not the down-regulation of CDH1 (P=ns). Furthermore, up-regulation of PLEKHA7 and PRDX4 together with down-regulation of TMSB10, and SERPINB5 allowed the differentiation between ILCs and luminal B IDCs (P<0.05). Expression differences were confirmed by immunohistochemistry for claudin 7, cytokeratin 5/6, E-cadherin and matrix metalloproteinase 2.
Conclusions: ILCs vs. IDC display down-regulation of genes related to proliferation, cell adhesion, actin cytoskeleton and ubiquitin proteins, and up-regulation of cell migration associated genes, ions binding and transport and to catabolic processes. PLEKHA7 and PRDX4, up-regulation and SERPINB5 and TMSB10 down-regulation allowed the differentiation between ILC and luminal B IDCs.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 14, Tuesday Afternoon