Histone deacetylase 3 promotes pancreatic cancer cell proliferation, invasion and increases drug-resistance through histone modification of P27, P53 and Bax.
Int J Oncol
; 45(4): 1523-30, 2014 Oct.
Article
in En
| MEDLINE
| ID: mdl-25070540
ABSTRACT
Pancreatic cancer is one of the most aggressive solid malignancies with a dismal survival rate. Recent studies have shown that high expression levels of histone deacetylase 3 (HDAC3) correlate with malignant phenotype. However, the expression patterns and biological role of HDAC3 in pancreatic cancer remain unclear. In this study, our data showed that a higher level of HDAC3 protein expression was found in pancreatic cancer as compared to paired paracancerous tissues. Consistently, higher expression level of HDAC3 was found in all of the eight pancreatic cancer cell lines relative to human pancreatic ductal epithelial cells (HPDE). In addition, further function analysis revealed that HDAC3 can function as oncogenic protein, which could promote pancreatic cancer cell proliferation, migration and invasion, and may increase drug resistance. Moreover, the functional involvement of HDAC3 was partially correlated with post-induction repression of P53, P27 and Bax gene transcription, acting via H3K9 deacetylation. Taken together, our data suggest that HDAC3 participates in the pathogenesis and progression of pancreatic cancer through histone modification, which might be a pivotal epigenetic target against this devastating disease.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Histones
/
Drug Resistance, Neoplasm
/
Histone Deacetylases
Limits:
Humans
Language:
En
Journal:
Int J Oncol
Journal subject:
NEOPLASIAS
Year:
2014
Document type:
Article