TY - JOUR
T1 - Integrated Analysis of Global mRNA and Protein Expression Data in HEK293 Cells Overexpressing PRL-1
AU - Dumaual, Carmen M.
AU - Steere, Boyd A.
AU - Walls, Chad D.
AU - Wang, Mu
AU - Zhang, Zhong Yin
AU - Randall, Stephen K.
PY - 2013/9/3
Y1 - 2013/9/3
N2 - Background:The protein tyrosine phosphatase PRL-1 represents a putative oncogene with wide-ranging cellular effects. Overexpression of PRL-1 can promote cell proliferation, survival, migration, invasion, and metastasis, but the underlying mechanisms by which it influences these processes remain poorly understood.Methodology:To increase our comprehension of PRL-1 mediated signaling events, we employed transcriptional profiling (DNA microarray) and proteomics (mass spectrometry) to perform a thorough characterization of the global molecular changes in gene expression that occur in response to stable PRL-1 overexpression in a relevant model system (HEK293).Principal Findings:Overexpression of PRL-1 led to several significant changes in the mRNA and protein expression profiles of HEK293 cells. The differentially expressed gene set was highly enriched in genes involved in cytoskeletal remodeling, integrin-mediated cell-matrix adhesion, and RNA recognition and splicing. In particular, members of the Rho signaling pathway and molecules that converge on this pathway were heavily influenced by PRL-1 overexpression, supporting observations from previous studies that link PRL-1 to the Rho GTPase signaling network. In addition, several genes not previously associated with PRL-1 were found to be significantly altered by its expression. Most notable among these were Filamin A, RhoGDIα, SPARC, hnRNPH2, and PRDX2.Conclusions and Significance:This systems-level approach sheds new light on the molecular networks underlying PRL-1 action and presents several novel directions for future, hypothesis-based studies.
AB - Background:The protein tyrosine phosphatase PRL-1 represents a putative oncogene with wide-ranging cellular effects. Overexpression of PRL-1 can promote cell proliferation, survival, migration, invasion, and metastasis, but the underlying mechanisms by which it influences these processes remain poorly understood.Methodology:To increase our comprehension of PRL-1 mediated signaling events, we employed transcriptional profiling (DNA microarray) and proteomics (mass spectrometry) to perform a thorough characterization of the global molecular changes in gene expression that occur in response to stable PRL-1 overexpression in a relevant model system (HEK293).Principal Findings:Overexpression of PRL-1 led to several significant changes in the mRNA and protein expression profiles of HEK293 cells. The differentially expressed gene set was highly enriched in genes involved in cytoskeletal remodeling, integrin-mediated cell-matrix adhesion, and RNA recognition and splicing. In particular, members of the Rho signaling pathway and molecules that converge on this pathway were heavily influenced by PRL-1 overexpression, supporting observations from previous studies that link PRL-1 to the Rho GTPase signaling network. In addition, several genes not previously associated with PRL-1 were found to be significantly altered by its expression. Most notable among these were Filamin A, RhoGDIα, SPARC, hnRNPH2, and PRDX2.Conclusions and Significance:This systems-level approach sheds new light on the molecular networks underlying PRL-1 action and presents several novel directions for future, hypothesis-based studies.
UR - http://www.scopus.com/inward/record.url?scp=84883312932&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0072977
DO - 10.1371/journal.pone.0072977
M3 - Article
C2 - 24019887
AN - SCOPUS:84883312932
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e72977
ER -