Upregulated histone deacetylase 1 expression in pancreatic ductal adenocarcinoma and specific siRNA inhibits the growth of cancer cells.
OBJECTIVE
So far, there are no investigations about the role of histone deacetylase 1 (HDAC1) in tumorigenesis of pancreatic ductal adenocarcinoma. This study was designed to elucidate the roles and mechanisms of HDAC1 in tumorigenesis of pancreatic ductal adenocarcinoma.


METHODS
Real-time reverse transcription-polymerase chain reaction and immunohistochemistry techniques were adopted to detect the expression of HDAC1 in human pancreatic ductal adenocarcinoma tissues and paired paracancerous tissues. The roles of HDAC1 in human pancreatic cell line PaTu8988 were investigated using siRNA.


RESULTS
Histone deacetylase 1 mRNA in pancreatic cancer tissues were significantly higher than in paracancerous tissues (P < 0.05). Immunohistochemistry showed that the indices of HDAC1 in pancreatic cancer tissues and paracancerous tissues were 56.4% (SD, 23.1%) and 6.7% (SD, 5.0%), respectively (P < 0.001). Knockdown of HDAC1 can generate a remarkable defect in proliferation and also can significantly induce apoptosis and S-phase arrest in PaTu8988 cells (P < 0.05). The Bcl-2 mRNA expression was significantly downregulated, whereas the p21 and Bax mRNA expression were significantly upregulated.


CONCLUSIONS
The HDAC1 overexpression might play an important role in tumorigenesis of pancreatic cancer. Our data support the development of selective inhibitors targeting HDAC1 for the treatment of pancreatic ductal adenocarcinoma. Histone deacetylase 1 could be a new gene therapy target in pancreatic ductal adenocarcinoma.
Gao
Dao-Jian
DJ
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Xu
Min
M
Zhang
Yu-Qi
YQ
Du
Yi-Qi
YQ
Gao
Jun
J
Gong
Yan-Fang
YF
Man
Xiao-Hua
XH
Wu
Hong-Yu
HY
Jin
Jing
J
Xu
Guo-Ming
GM
Li
Zhao-Shen
ZS
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D056284:Histone Deacetylase 1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics*; D015854:Up-Regulation
D012333:RNA, Messenger; D034741:RNA, Small Interfering; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1