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Series GSE42979 Query DataSets for GSE42979
Status Public on Dec 19, 2012
Title PIAS3 induction of apoptosis in non-small cell lung cancer cells is p53-independent and has STAT3-independent mediator.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Protein inhibitor of activated STAT3 (PIAS3) is an endogenous inhibitor of STAT3 that negatively regulates STAT3 transcriptional activity and cell growth and demonstrates limited expression in the majority of human squamous cell carcinomas of the lung. In the present study we sought to determine if PIAS3 inhibits cell growth in non-small cell lung cancer (NSCLC) cell lines by induction of apoptosis and further determine the dependence of PIAS3 activity on p53 status by using both wild-type and p53-null cells. Our results demonstrate that over-expression of PIAS3 promotes caspase 3 activation and PARP cleavage. Furthermore, the expression of pro-survival family members Bcl-xL and Bcl-2 is decreased. These effects were observed after both transient and regulated expression of exogenous PIAS3 and were independent of p53 status. Furthermore, while p53 can promote apoptosis by inhibition of STAT3 activity, PIAS3 inhibition of STAT3 activity was also p53 independent. Microarray experiments were performed to further investigate the STAT3-dependence of PIAS3-induced apoptosis by comparing the apoptotic gene expression signature induced by PIAS3 over-expression with that induced by STAT3 siRNA. The results showed that a subset of apoptotic genes, including CIDEC and DAPK2, were uniquely expressed only after PIAS3 expression. Thus, PIAS3 may represent a promising lung cancer therapeutic target because of its p53-independent efficacy as well as its potential to synergize with direct STAT3 inhibitors.
 
Overall design The expression profiles of genes related to apoptosis in A549 cell line transfected with pCMV5 vector encoding human PIAS3 compared with that induced by STAT3 siRNA
Cells in all three groups were grown in serum-free medium, then stimulated with EGF, then one group transfected with pCMV5 vector encoding human PIAS3, second group was induced by STAT3 siRNA, third group considered as control.
 
Contributor(s) Dabir S, Kluge A, Liu Y, Halmos B, Wildey G, Dowlati A
Citation(s) 23959540
Submission date Dec 18, 2012
Last update date Dec 06, 2018
Contact name yu liu
E-mail(s) yxl442@case.edu
Organization name Case Western Reserve University
Street address 11900 Euclid
City Cleveland
ZIP/Postal code Ohio
Country USA
 
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (6)
GSM1054353 A549_siRNA_STAT3_rep1
GSM1054354 A549_siRNA_STAT3_rep2
GSM1054355 A549_PIAS3_rep1
Relations
BioProject PRJNA184013

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE42979_RAW.tar 12.1 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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