Splice variant PRKC-ζ(-PrC) is a novel biomarker of human prostate cancer.
BACKGROUND
Previously, using gene-knockdown techniques together with genome expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ) to mediate the malignant phenotype of human prostate cancer. However, according to NCBI, the gene has undergone several major iterations. Therefore, to understand the relationship between its structure and biological activities, we have analysed its expressed sequence in prostate cancer cell lines and tissues.


METHODS
Transcriptome-walking and targeted PCR were used to sequence the mRNA transcribed from PRKCZ. Hydropathy analysis was employed to analyse the hypothetical protein sequence subsequently translated and to identify an appropriate epitope to generate a specific monoclonal antibody.


RESULTS
A novel sequence was identified within the 3'-terminal domain of human PRKCZ that, in prostate cancer cell lines and tissues, is expressed during transcription and thereafter translated into protein (designated PKC-ζ(-PrC)) independent of conventional PKC-ζ(-a). The monoclonal antibody detected expression of this 96 kD protein only within malignant prostatic epithelium.


CONCLUSIONS
Transcription and translation of this gene sequence, including previous intronic sequences, generates a novel specific biomarker of human prostate cancer. The presence of catalytic domains characteristic of classic PKC-β and atypical PKC-ι within PKC-ζ(-PrC) provides a potential mechanism for this PRKCZ variant to modulate the malignant prostatic phenotype out-with normal cell-regulatory control.
Division of Pathology, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 6th Floor, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
S
S
Yao
S J
SJ
Ireland
A
A
Bee
C
C
Beesley
S S
SS
Forootan
A
A
Dodson
T
T
Dickinson
P
P
Gerard
L-Y
LY
Lian
J M
JM
Risk
P
P
Smith
M I
MI
Malki
Y
Y
Ke
C S
CS
Cooper
C
C
Gosden
C S
CS
Foster
D000595:Amino Acid Sequence; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D059467:Transcriptome / Q000235:genetics; D000099221:Protein Kinase C zeta
D014408:Biomarkers, Tumor; D011493:Protein Kinase C; D012333:RNA, Messenger; D000099221:Protein Kinase C zeta