Interference with ATF5 function enhances the sensitivity of human pancreatic cancer cells to paclitaxel-induced apoptosis.
BACKGROUND
Past work has established that human glioblastomas and breast cancer cells invariably express the activating transcription factor 5 (ATF5) and that loss of function of ATF5 caused massive apoptotic death of all cancer cell lines tested. ATF5 expression and function in pancreatic cancer cells have not been investigated.


METHODS
Quantitative real-time/reverse transcription-polymerase chain reaction (QRT/RT-PCR), western blotting (WB), immunohistochemistry (IHC) and promoter reporter assay were used for gene expression analysis. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS (fluorescence-activated cell sorting) analysis were used to monitor cell viability/apoptosis.


RESULTS
ATF5 is highly expressed in pancreatic cancer cells as compared with non-tumor tissues. Both paclitaxel treatment and loss of function of ATF5 elicited apoptosis of SW1990 cells. Interference with ATF5 function in SW1990 cells resulted in down-regulation of BCL-2 and up-regulation of BAX, resulting in enhanced sensitivity to apoptosis induced by paclitaxel treatment.


CONCLUSIONS
ATF5 is highly expressed in pancreatic cancer cells. Targeting ATF5 significantly enhances paclitaxel-induced apoptosis in human pancreatic cancer cells. ATF5 could be an important therapeutic target for pancreatic cancer treatment.
Department of Neural and Behavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Ming
M
Hu
Bin
B
Wang
Dongmeng
D
Qian
Ling
L
Li
Li
L
Zhang
Xuxia
X
Song
David X
DX
Liu
D051696:Activating Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
C507532:ATF5 protein, human; D051696:Activating Transcription Factors; D000970:Antineoplastic Agents; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D017239:Paclitaxel