Unknown

Dataset Information

0

Epigenetic inactivation of inositol polyphosphate 4-phosphatase B (INPP4B), a regulator of PI3K/AKT signaling pathway in EBV-associated nasopharyngeal carcinoma.


ABSTRACT: Nasopharyngeal carcinoma (NPC) is a common viral-associated neoplasm in which multiple signaling cascades are interfered with by Epstein-Bar virus (EBV) latent proteins and various genetic alterations. Aside from the previously reported PIK3CA amplification, we examined the role of INPP4B, a negative regulator of the PI3K/AKT signaling pathway in the development of NPC. By RT-PCR and Western blotting, we revealed that the expression of INPP4B was down-regulated in all five established EBV-positive tumor lines. While INPP4B was consistently expressed in normal nasopharyngeal epithelial cells, downregulation of INPP4B was found in 32/65 (49.2%) of primary tumors by immunohistochemistry. Furthermore, our study also demonstrated the hypermethylation of the 5'CpG island of INPP4B in the tumors in which INPP4B transcription was downregulated. Notably, the re-expression of INPP4B was detected in the NPC cells treated with the demethylation agent (5-aza-2'deoxycytidine). Our study showed that promoter hypermethylation was the major mechanism for transcriptional silencing of INPP4B in NPC. Furthermore, restoration of INPP4B expression significantly suppressed PI3K/AKT downstream signals in the NPC C666-1 cells. In vivo growth inhibition was clearly demonstrated in the tumor cells stably expressing INPP4B. The findings indicate that epigenetic inactivation of INPP4B is one of the key mechanisms in activating PI3K/AKT signaling cascade and playing a role in the tumorigenesis of NPC.

SUBMITTER: Yuen JW 

PROVIDER: S-EPMC4134277 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3508174 | biostudies-literature
| S-EPMC10783437 | biostudies-literature
| S-EPMC3009830 | biostudies-other
| S-EPMC3204353 | biostudies-literature
| S-EPMC2957372 | biostudies-literature
| S-EPMC4785718 | biostudies-literature
| S-EPMC1356573 | biostudies-literature
| S-EPMC10197106 | biostudies-literature
| S-EPMC312749 | biostudies-literature
| S-EPMC6377303 | biostudies-literature