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Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons

Nagano, K, Masters, JR, Akpan, A, Yang, A, Corless, S, Wood, C, Hastie, C, Zvelebil, M, Cramer, R and Naaby-Hansen, S (2004) Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons Oncogene, 23 (9). pp. 1693-1703.

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Abstract

Protein expression and de novo synthesis in normal and prostate cancer cell lines derived from the same patient were compared by proteomic analysis, and the effects of INFalpha and INFgamma (INF=interferon) determined. The expressions of several INF-inducible proteins, including MxA, Nmi, PA28a and IFP53, were downregulated in the cancer cells. INFgamma induced a more than twofold increase or decrease in the synthesis rates of almost twice as many proteins in the cancer cell line. The positive regulator of INF-induced transcription ISGF3gamma was upregulated in the cancer cells and inversely regulated by INFalpha and INFgamma in the normal and cancer cells. Moreover, ISGF3gamma's induction by INFgamma in the cancer cells was more enhanced by simultaneous stimulation with EGF, than its induction in the normal cells. In all, 31 differentially regulated proteins were identified by mass spectrometry analysis, several of which are involved in chaperone-assisted protein folding in the endoplasmic reticulum (ER) or in regulated protein degradation. Our results suggest that the exclusion of proteins by the ER quality control system, crosstalk between the EGF- and INF-induced signalling pathways and the regulation of INF-inducible genes are all altered in the prostate cancer cells. The combination of upregulated activity in the growth-promoting PI3K/Akt pathway, suppression of Nmi and overexpression of hnRNP-K and c-myc proteins may explain why the prostate cancer cells were found to be more resistant to the growth inhibitory effects of INFgamma.

Item Type: Article
Authors :
NameEmailORCID
Nagano, KUNSPECIFIEDUNSPECIFIED
Masters, JRUNSPECIFIEDUNSPECIFIED
Akpan, AUNSPECIFIEDUNSPECIFIED
Yang, AUNSPECIFIEDUNSPECIFIED
Corless, SUNSPECIFIEDUNSPECIFIED
Wood, CUNSPECIFIEDUNSPECIFIED
Hastie, CUNSPECIFIEDUNSPECIFIED
Zvelebil, MUNSPECIFIEDUNSPECIFIED
Cramer, RUNSPECIFIEDUNSPECIFIED
Naaby-Hansen, SUNSPECIFIEDUNSPECIFIED
Date : 2004
Uncontrolled Keywords : 1-Phosphatidylinositol 3-Kinase/metabolism Carrier Proteins/metabolism Cell Division/drug effects Cell Line Cell Line, Tumor DNA-Binding Proteins/biosynthesis Electrophoresis, Gel, Two-Dimensional Epidermal Growth Factor/pharmacology GTP-Binding Proteins/biosynthesis *Gene Expression Profiling Gene Expression Regulation, Neoplastic/*drug effects Heterogeneous-Nuclear Ribonucleoprotein K/biosynthesis Humans Interferon-Stimulated Gene Factor 3 Interferon-Stimulated Gene Factor 3, gamma Subunit Interferon-alpha/*pharmacology Interferon-gamma/*pharmacology *Intracellular Signaling Peptides and Proteins Male Mitogen-Activated Protein Kinases/metabolism Phosphorylation/drug effects Prostate/cytology/*metabolism/pathology Prostatic Neoplasms/enzymology/*metabolism/pathology Proteome/*biosynthesis Signal Transduction/drug effects Spectrometry, Mass, Electrospray Ionization Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Transcription Factors/biosynthesis
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:14
Last Modified : 17 May 2017 09:14
URI: http://epubs.surrey.ac.uk/id/eprint/822886

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