Rabbit Anti-Human IFNE (a.a. 101-200) Polyclonal antibody

The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (Ml) primary tumors, highlighting a major mechanism(s) contributing to cancer associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study the pharmacogenomics of BCa.

Interferon epsilon (IFNE) is type I interferon which stands out through its unusual expression profile and differing regulation compared to classic type I interferons such as interferon alpha and interferon beta. Unlike other type I interferons, the expression of IFNE is not stimulated through exposure to viral agents. Expression of IFNE is most abundant in mouse and human endometrium where it is constitutively expressed in luminal and glandular epithelial cells and expression levels are up-regulated with estrogen exposure. The aim of the current study was to determine whether a cycle or pregnancy dependent expression pattern of IFNE is existent in equine endometrium and to localize IFNE expression within the endometrium. Additionally, endometrial explant culture and culture of mixed epithelial/stromal cells populations was used to determine the effects estrogen and seminal plasma on IFNE transcript abundance. Samples collected during diestrus and pregnancy expressed significantly higher levels of IFNE than samples obtained from anestrous or estrous mares (P < 0.001). Exposure of mixed endometrial epithelial/stromal cell populations and endometrial explants to 10% seminal plasma and estradiol 17 beta did not affect IFNE expression levels (P > 0.05). Upon in situ hybridization, staining was exclusively present in luminal and glandular epithelial cells, with stromal displaying absent staining intensity. Both diestrous and pregnant samples were characterized by markedly stronger staining of glandular epithelial cells than anestrous and estrous samples. The progesterone-dependent increase in IFNE abundance during the estrous cycle likely implies that IFNE is part of the innate immune system in endometrium that gives protection against uterine infections during progesterone-dominated phase of the estrous cycle.