Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma.
Identification of gene products exclusively or abundantly expressed in cancer may yield novel tumour markers. We recently isolated a number of cDNA clones, including alpha-prothymosin, from rat hepatocellular carcinoma (HCC) using a subtraction-enhanced display technique. Alpha-Prothymosin is involved in cell proliferation and is regulated by the oncogene c-myc in vitro. In the present study, we analysed alpha-prothymosin gene expression and its correlation with c-myc in patients with HCC, cirrhosis and adenoma and in normal controls. Hepatic alpha-prothymosin messenger RNA (mRNA) levels were two- to 9.2-fold higher in tumoral tissues than in adjacent non-tumoral tissues in 14 of 17 patients with HCC, regardless of coexisting cirrhosis and viral hepatitis. No marked difference in alpha-prothymosin mRNA levels was present in patients with adenoma and hepatic cirrhosis and in healthy controls. The c-myc mRNA amounts were two- to fivefold increased in 11 of 17 patients with HCC and correlated significantly with those of alpha-prothymosin (P < 0.001). In situ hybridization revealed that increased alpha-prothymosin mRNA was localized in the tumour nodules of the patients with HCC. These data suggest that overexpression of alpha-prothymosin in HCC patients, correlated with c-myc, is possibly involved in the tumorigenic process and may be a novel molecular marker for human HCC.
Wu
C G
CG
Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Habib
N A
NA
Mitry
R R
RR
Reitsma
P H
PH
van Deventer
S J
SJ
Chamuleau
R A
RA
D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000378:metabolism; D006526:Hepatitis C / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism
D014408:Biomarkers, Tumor; D011498:Protein Precursors; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C040782:prothymosin alpha; D013947:Thymosin