| Summary: | <p>The mechanism of progression from ductal carcinoma <i>in situ</i> (DCIS) to invasive ductal carcinoma (IDC) remains largely unknown. We compared gene expression in tumors with simultaneous DCIS and IDC to decipher how diverse proteins participate in the local invasive process.</p><p>Twenty frozen tumor specimens with concurrent, but separated, DCIS and IDC were microdissected and evaluated. Total RNA was extracted and microarray analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Microarray data were validated by quantitative real time reverse transcription-PCR (qRT-PCR) and immunohistochemistry. Controls included seven pure <i>in situ</i> carcinomas, eight fragments from normal breast tissue, and a series of mouse breast carcinomas (MMTV-PyMT).</p><p>Fifty-six genes were differentially expressed between DCIS and IDC samples. The genes upregulated in IDC samples, and probably associated with invasion, were related to the epithelial-mesenchymal transition (<i>ASPN, THBS2, FN1, SPARC, </i>and <i>COL11A1</i>), cellular adhesion (<i>GJB2</i>), cell motility and progression (<i>PLAUR, PLAU, BGN, ADAMTS16, </i>and <i>ENPP2</i>), extracellular matrix degradation (<i>MMP11, MMP13, </i>and <i>MMP14</i>), and growth/proliferation (<i>ST6GAL2</i>). qRT-PCR confirmed the expression patterns of <i>ASPN, GJB2, ENPP2, ST6GAL2,</i> and <i>TMBS10</i>. Expression of the <i>ASPN </i>and<i> GJB2 </i>gene products was detected by immunohistochemistry in invasive carcinoma foci. The association of GJB2 protein expression with invasion was confirmed by qRT-PCR in mouse tumors <i>(P < </i>0.05).</p><p><b>Conclusions:</b> The upregulation of <i>ASPN and GJB2</i> may play important roles in local invasion of breast ductal carcinomas.</p>
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