Functional Correlates of Jab1 Networks in Triple Negative Breast Cancer
Mark M Sasamoto, Thuy T Vu, Francois X Claret, Mary E Edgerton. UT MD Anderson Cancer Center, Houston, TX
Background: Jab1 (c-Jun activation domain-binding protein 1) (also know as COPS5/CSN5) has been demonstrated to cause low levels of p27, a cell cycle checkpoint, thus promoting proliferative behavior. Aberrant expression has been reported in metastatic breast cancer compared with low or absent levels in normal breast tissue. We have found that Jab1 mRNA is elevated in approximately 50% of triple negative breast cancer (TNBC) patients, indicating a possible role for regulation of Jab1 as a therapy in TNBC. We present results from a study of gene expression patterns associated with Jab1 in TNBC.
Design: Using Backward Chaining Rule Induction (BCRI), a network inference strategy that we introduced previously, we identify other agents associated with JAB1 activity in TNBC. BCRI was applied in a cohort of 99 patients compiled from the literature. We examined the persistence of thee relationships in The Cancer Genome Atlas (TCGA) data, and reviewed the annotation and known relationships between Jab1 and these other genes.
Results: High levels of RRS1, TGS1, C8orf33, SIAHBP1, HSF1, and EXOSC4 predict high levels of Jab1 in the TNBC data. The TCGA data only contains only RRS1 and TGS1, which maintain a correlation with Jab1. RRS1 is involved in spindle organization, while TGS1, C8orf33, SIAHBP1, and EXOC4 play a role in mRNA processing. The relationship with HSF1 is not clear. HSF1 has been associated with Her2neu activity in breast cancer.
Conclusions: Data mining of TNBC to explore relationships involving Jab1 are important in the development of efforts to target Jab1 as a potential therapy in TNBC and other aggressive breast cancer. We have found some interesting relationships, possibly downstream (RRS1, TGS1, C8orf33, SIAHBP1 and EXOSC4) and another that is possible additive (HSF1).
An additive factor might introduce resistance to therapy. These relationships require further study.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 283, Tuesday Morning