Profiling the transcriptomes

Profiling the transcriptomes of cancer tissues and cell lines has significantly advanced our knowledge in the biology of TNBC and potential therapeutic targets, how ever, it remains obscure how posttranscriptional changes in tumor suppressors or oncoproteins contribute to the development of TNBC. Smurf2 is a HECT family ubiquitin ligase, which has been implicated in diverse biological functions in cluding the transforming growth factor beta signaling, mitotic regulation, cell polarity, motility and chromatin modifications. According to the literature, Smurf2 appears to play complex roles in tumorigenesis. A previous study using immunohistochemistry showed that esophageal squamous cell carcinomas expressed high levels of Smurf2, which correlated with poor prog nosis.

Another study on lung adenocarcinomas and head neck carcinomas Inhibitors,Modulators,Libraries showed a positive correlation between Smurf2 protein levels and EGFR protein Inhibitors,Modulators,Libraries levels. In contrast, there have been several reports demon strating decreased expression of Smurf2 in other types of cancer. Protein levels of Smurf2 were Inhibitors,Modulators,Libraries found to be downregulated in human lymphoma and breast cancer tissues relative to non cancer tissues. In a study on prostate cancers, Smurf2 mRNA levels were lower in ad vanced tumors compared to less advanced organ confined tumors, suggesting association of Smurf2 downregulation with tumor progression. Importantly, two recent studies using Smurf2 null mice have shown that Smurf2 deficiency increases susceptibility to spontaneous tumorigenesis in various tissues including the liver, lung, pituitary and mam mary gland.

The activity of Smurf2 to ubiquitinate and degrade RNF20, a RING family E3 that controls Inhibitors,Modulators,Libraries histone H2B ubiquitination and genome stability, has been impli cated for the tumor suppressive role of Smurf2. In this study we demonstrate that human TNBC tis sues express significantly lower levels of Smurf2 protein relative to normal mammary tissues, ductal carcinomas in situ and ER PR breast cancer tissues. We also Inhibitors,Modulators,Libraries have revealed that microRNAs such as miR 15a, miR 15b, miR 16 and miR 128, whose expression is increased by inactivating mutations of the retinoblast oma gene, downregulate translation of Smurf2 pro tein in TNBC cells. These results suggest that Smurf2 downregulation is an event associated with RB loss and microRNA deregulation during the progression of TNBC, and likely involved in the aggressive phenotypes.

Methods Patients Surgical specimens were obtained from breast cancer pa tients who had mastectomy or lumpectomy at Louisiana State University Health Sci ences Center, Shreveport, LA, during the period between 2002 and 2010. This study was reviewed and approved in advance by the Institutional Review Boards of the Louisiana selleck compound State University Health Sciences Center and the Feinberg School of Medicine, Northwestern University.

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