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

Autor: Alice Yang, Soren Naaby-Hansen, Kohji Nagano, Markéta J.J.M. Zvelebil, Christopher Barry Wood, John R. W. Masters, Steve Corless, Claire Hastie, Akunna Akpan, Rainer Cramer
Rok vydání: 2003
Předmět:
Male
Myxovirus Resistance Proteins
Spectrometry
Mass
Electrospray Ionization
Cancer Research
medicine.medical_specialty
Proteome
Protein degradation
Biology
medicine.disease_cause
Cell Line
Heterogeneous-Nuclear Ribonucleoprotein K
Interferon-gamma
Phosphatidylinositol 3-Kinases
Prostate cancer
GTP-Binding Proteins
Interferon
Cell Line
Tumor
Internal medicine
Genetics
medicine
Humans
Electrophoresis
Gel
Two-Dimensional
Phosphorylation
Molecular Biology
PI3K/AKT/mTOR pathway
Epidermal Growth Factor
Gene Expression Profiling
Endoplasmic reticulum
Intracellular Signaling Peptides and Proteins
Prostate
Interferon-alpha
Prostatic Neoplasms
Cancer
Interferon-Stimulated Gene Factor 3
medicine.disease
Interferon-Stimulated Gene Factor 3
gamma Subunit
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Endocrinology
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Cancer cell
Cancer research
Mitogen-Activated Protein Kinases
Carrier Proteins
Carcinogenesis
Cell Division
Signal Transduction
Transcription Factors
medicine.drug
Zdroj: Oncogene. 23:1693-1703
ISSN: 1476-5594
0950-9232
DOI: 10.1038/sj.onc.1207297
Popis: 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.
Databáze: OpenAIRE
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