Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma.

Détails

ID Serval
serval:BIB_DCD05FDCB236
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma.
Périodique
Cancer Research
Auteur(s)
Zhang L., Huang J., Yang N., Liang S., Barchetti A., Giannakakis A., Cadungog M.G., O'Brien-Jenkins A., Massobrio M., Roby K.F., Katsaros D., Gimotty P., Butzow R., Weber B.L., Coukos G.
ISSN
0008-5472 (Print)
ISSN-L
0008-5472
Statut éditorial
Publié
Date de publication
2006
Volume
66
Numéro
9
Pages
4627-4635
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
The protein kinase C (PKC) family plays a key regulatory role in a wide range of cellular functions as well as in various cancer-associated signal transduction pathways. Here, we investigated the genomic alteration and gene expression of most known PKC family members in human ovarian cancer. The DNA copy number of PKC family genes was screened by a high-resolution array-based comparative genomic hybridization in 89 human ovarian cancer specimens. Five PKC genes exhibited significant DNA copy number gains, including PKCiota (43.8%), PKCbeta1 (37.1%), PKCgamma (27.6%), PKCzeta (22.5%), and PKCtheta (21.3%). None of the PKC genes exhibited copy number loss. The mRNA expression level of PKC genes was analyzed by microarray retrieval approach. Two of the amplified PKC genes, PKCiota and PKCtheta, were significantly up-regulated in ovarian cancer compared with normal ovary. Increased PKCiota expression correlated with tumor stage or grade, and PKCiota overexpression was seen mostly in ovarian carcinoma but not in other solid tumors. The above results were further validated by real-time reverse transcription-PCR with 54 ovarian cancer specimens and 24 cell lines; overexpression of PKCiota protein was also confirmed by tissue array and Western blot. Interestingly, overexpressed PKCiota did not affect ovarian cancer cell proliferation or apoptosis in vitro. However, decreased PKCiota expression significantly reduced anchorage-independent growth of ovarian cancer cells, whereas overexpression of PKCiota contributed to murine ovarian surface epithelium transformation in cooperation with mutant Ras. We propose that PKCiota may serve as an oncogene and a biomarker of aggressive disease in human ovarian cancer.
Mots-clé
Cell Growth Processes/physiology, Cell Line, Tumor, Cell Transformation, Neoplastic/genetics, Cell Transformation, Neoplastic/metabolism, Cisplatin/pharmacology, Cisplatin/therapeutic use, Drug Resistance, Neoplasm, Female, Gene Dosage, Humans, Isoenzymes/biosynthesis, Isoenzymes/genetics, Mutation, Ovarian Neoplasms/drug therapy, Ovarian Neoplasms/enzymology, Protein Kinase C/biosynthesis, Protein Kinase C/genetics, RNA, Messenger/biosynthesis, RNA, Messenger/genetics, Transcription, Genetic, Transfection, Tumor Markers, Biological/genetics, Up-Regulation, ras Proteins/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/10/2014 11:42
Dernière modification de la notice
20/08/2019 16:01
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