Meta-analysis of oncogenic protein kinase Ciota signaling in lung adenocarcinoma.
OBJECTIVE
Atypical protein kinase Ciota (PKCiota) is an oncogene in non-small cell lung cancer (NSCLC). Here, we identify four functional gene targets of PKCiota in lung adenocarcinoma (LAC), the most prominent form of NSCLC.


METHODS
Three independent public domain gene expression data sets were interrogated to identify genes coordinately expressed with PKCiota in primary LAC tumors. Results were validated by QPCR in an independent set of primary LAC tumors. RNAi-mediated knockdown of PKCiota and the target genes was used to determine whether expression of the identified genes was regulated by PKCiota, and whether these target genes play a role in anchorage-independent growth and invasion of LAC cells.


RESULTS
Meta-analysis identified seven genes whose expression correlated with PKCiota in primary LAC. Subsequent QPCR analysis confirmed coordinate overexpression of four genes (COPB2, ELF3, RFC4, and PLS1) in an independent set of LAC samples. RNAi-mediated knockdown showed that PKCiota regulates expression of all four genes in LAC cells, and that the four PKCiota target genes play an important role in the anchorage-independent growth and invasion of LAC cells. Meta-analysis of gene expression data sets from lung squamous cell, breast, colon, prostate, and pancreas carcinomas, as well as glioblastoma, revealed that a subset of PKCiota target genes, particularly COPB2 and RFC4, correlate with PKCiota expression in many tumor types.


CONCLUSIONS
Meta-analysis of public gene expression data are useful in identifying novel gene targets of oncogenic PKCiota signaling. Our data indicate that both common and cell type-specific signaling mechanisms contribute to PKCiota-dependent transformation.
Erdogan
Eda
E
Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
Klee
Eric W
EW
Thompson
E Aubrey
EA
Fields
Alan P
AP
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D053263:Gene Regulatory Networks; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D034741:RNA, Small Interfering / Q000494:pharmacology; D051818:Replication Protein C / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099293:Protein Kinase C-lambda
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D011493:Protein Kinase C; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D034741:RNA, Small Interfering; D051818:Replication Protein C; D014157:Transcription Factors; D000099293:Protein Kinase C-lambda; C105529:ELF3 protein, human; C497563:RFC4 protein, human; C026742:plastin