ASPN, GJB2, ENPP2, ST6GAL2 and TMSB10 Are Related with Invasiveness in Ductal Breast Carcinomas.
Barbara Castellana, Elena Serrano, Gloria Peiro, Belen Ojeda, Carmen Alonso, Tania Vazquez, Josefina Munoz, Agusti Barnadas, Enrique Lerma. Hospital de la Santa Creu i Sant Pau. Universitat Autònoma, Barcelona, Spain; Hospital de Alicante, Spain
Background: The mechanism of progression from in situ ductal carcinoma (DCIS) to invasive ductal carcinoma (IDC) remains largely unknown. We compared gene expression patterns in simultaneous in situ and invasive areas of ductal carcinomas to obtain insight into the molecular basis for the invasiveness.
Design: We performed differential gene expression profiling using microarray analysis in 21 tumors. Careful dissection was done to obtain separately foci of DCIS and IDC. mRNA was extracted by standard procedure and purified. The mRNA concentration and quality was assessed by mRNA 6000 Nano LabChip Kit (Agilent Bioanalyzer). Samples were analyzed upon Affymetrix GeneChip®Human Gene 1.0 ST Array. We surveyed the expression of 10 differentially expressed genes asporin (ASPN),cytokeratin5 (KRT5),maspin (SERPINB5),connexin26 (GJB2), ST6 beta-galactosamide alpha-2,6-sialyltranferase 2 (ST6GAL2), Autotaxin (ENPP2),vimentin (VIM),E-cadherin (CDH1),peroxiredoxin4 (PRDX4),thymosin beta10 (TMSB10).
Results: Invasiveness was associated with: 1) up-regulation of several genes related to epithelial-mesenchymal transition (ASPN, THBS2, FN1, SPARC, COL11A1), cell motility and progression (PLAUR, PLAU, BGN, ADAMTS16, ENPP2), extracellular matrix degradation (MMP11, MMP13, MMP14) and growth/proliferation (ST6GAL2, GJB2) and 2) down regulation of genes related to cell adhesion (TNXB, TNXA, FVIII) and intermediate filaments cytoskeleton (KRT5) (all P<0.05). Differential gene expression was confirmed by real time-PCR analysis in ASPN, GJB2, ENPP2, ST6GAL2, KRT5, VIM and TMBS10 (P<0.05).
Conclusions: ASPN, GJB2, ENPP2, ST6GAL2 and TMSB10 were highly up-regulated in IDC compared with DCIS. Therefore, these genes may be potentially involved in the mechanisms of invasion from DCIS to IDC.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 15, Tuesday Afternoon