Abstract:
:Signal transducer and activator of transcription 5b (STAT5b) is likely the relevant STAT5 isoform with respect to the process of malignant progression in gliomas. STAT5b is a latent cytoplasmic protein involved in cell signaling through the modulation of growth factors, apoptosis, and angiogenesis. Previous in vitro studies have shown increased STAT5b expression in glioblastomas relative to low-grade tumors and normal brain. We recently demonstrated that phosphorylated STAT5b associates with delta epidermal growth factor receptor in the nucleus and subsequently binds the promoters of downstream effector molecules, including aurora kinase A. Analysis of TCGA dataset reveals that STAT5b is predominantly expressed in proneural (PN) gliomas relative to mesenchymal and neural gliomas. Here, we modeled ectopic expression of STAT5b in vivo using a platelet-derived growth factor subunit B (PDGFB)-dependent mouse model of PN glioma to determine its effect on tumor formation and progression. We showed that coexpression of STAT5b and PDGFB in mice yielded a significantly higher rate of high-grade gliomas than PDGFB expression alone. We also observed shorter survival in the combined expression set. High-grade tumors from the STAT5b + PDGFB expression set were found to have a lower rate of apoptosis than those from PDGFB alone. Furthermore, we showed that increased expression of STAT5b + PDGFB led to increased expression of downstream STAT5b targets, including Bcl-xL, cyclin D1 and aurora kinase A in high-grade tumors when compared to tumors derived from PDGFB alone. Our findings show that STAT5b promotes the malignant transformation of gliomas, particularly the PN subtype, and is a potential therapeutic target.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Gressot LV,Doucette TA,Yang Y,Fuller GN,Heimberger AB,Bögler O,Rao A,Latha K,Rao Gdoi
10.1002/ijc.29264subject
Has Abstractpub_date
2015-05-01 00:00:00pages
2047-54issue
9eissn
0020-7136issn
1097-0215journal_volume
136pub_type
杂志文章abstract::Prolonged culture of hepatocytes isolated from mouse liver results in the spontaneous development of colonies of liver epithelial cells that can proliferate indefinitely in vitro. We established 5 such cell lines from C3H/HeJ mice (C3H) and 22 cell lines from C3H/HeJ x C57BL/6J F1 mice (C3B6F1) to investigate whether ...
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