lack of comedo-necrosis in DCIS. All of the models of DCIS used in the present study lack ER and PR expression and represent 9 RNA-Seq of Breast Ductal Carcinoma In Situ Models 
aggressive disease for which conventional anti-estrogen therapies would not be used. Her-2/ neu amplification plays an important role in initiation rather than in progression of ductal carcinoma and its (-)-Blebbistatin web overexpression predicts local recurrence. SUM225 cells have amplification of Her2/neu. A direct positive relationship has been observed for the expression of ER, PR, and Bcl-2. Ringberg et al. suggest that a molecular signature with lack of ER and PR, Her2 overexpression, accumulation of p53, and high ki67 expression is a strong predictor of local recurrence rate in DCIS. In a retrospective study of DCIS cases, DCIS lesions that were positive for p16, COX-2, and Ki67 expression were significantly associated with risk of subsequent invasive cancer whereas DCIS lesions that either lacked ER but were positive for ERBB2 and Ki67 or that lacked COX2 and were positive for p16 and Ki67 were associated with recurrence of DCIS. Differentially Expressed Genes in Models of DCIS Sequencing revealed many novel differentially expressed transcripts in DCIS. The hierarchical clustering of samples indicates the robustness of the data and the reproducibility of the biological replicates. The observation that MCF10.DCIS has more genes in common with MCF10A than with either SUM102 or SUM225 is consistent with the fact that MCF10.DCIS and MCF10A are isogenic. The implication of the majority of the differentially expressed genes in the processes of cell-cell adhesion, cell proliferation and movement signify the importance of deregulation of these processes very early in the course of premalignant progression. Interestingly, several of the ten most down regulated molecules in the list of significantly differentially expressed genes pertain to the functions of cell adhesion and include CADM3, DPT, NID1 and TGFBI. The latter is consistent with the previous observation that the level of TGFBI decreases in progression from benign breast tissues to DCIS and IDC. TGFBI activates adhesion- 10 RNA-Seq of Breast Ductal Carcinoma In Situ Models associated signaling and decreases the motility in breast cancer cells both in vitro and in vivo. It also reduces the activation of matrix metalloproteinases 2 and 9, which are responsible for the degradation of extracellular matrix. In contrast to decreased TGFBI that has previously been associated with DCIS, decreased CADM3, DPT, and NID1 have not previously been linked to breast cancer. CADM3 also known as nectin like protein 1 is a cell-cell adhesion molecule and has been reported to suppress tumorigenicity in colon cancer cells. Loss of its expression has been detected in various gliomas. DPT is involved in cell adhesion and promotes ECM assembly. Downregulation of DPT has been previously observed in oral squamous cell carcinoma and is associated with lymph node metastasis. Decreased expression of DPT in hepatocellular carcinoma has also been reported. We also observed greater than tenfold down regulation in expression levels of NID1. Nidogens provide structural stability to basement membrane by connecting laminin and collagen IV networks. They interact with various integrins and play an important role in cell adhesion. Loss of nidogen expression weakens the basement membrane and favors invasion. A study by Ulazzi and co-workers reported that loss of
