p73 is up-regulated in a subset of hepatocellular carcinomas.
Loss of heterozygosity (LOH) at 1p36 occurs in a number of solid tumors including hepatocellular carcinoma (HCC). Recently, a novel gene, p73, has been identified at 1p36.33. p73 is structurally and functionally related to p53 located at 17p13.1, which is a target for inactivation in HCCs. p73 produces at least two splicing variants, p73alpha and beta, and a polymorphism in exon 2 results in two alleles, GC or AT. Initially, only the AT allele and p73alpha transcripts were identified in malignant cell lines, suggesting a role for these in the malignant phenotype. The aims of this study were to determine the extent of LOH at 1p36 and 17p13.1 in HCCs from Australia and South Africa, and to identify patterns of p73 mRNA and p73 and p53 protein expression. LOH at 1p36 was found in 8 of 25 Australian and 6 of 10 South African cases. p73 mRNA expression occurred in 8 HCCs, but not in nonmalignant liver tissue. Two of these 8 HCCs had LOH of 1p36. Both alpha and beta transcripts were observed in GC/GC homozygotes and GC/AT heterozygotes. No p73 protein expression was observed by immunohistochemistry in nonmalignant liver tissue or in HCC. p53 inactivation appeared to be associated with up-regulation of p73 expression, suggesting a compensatory role for p73 in this situation. The LOH at 1p36 implies a liver-specific tumor suppressor gene is in this region. However, the up-regulation of p73 mRNA suggests p73 is not the target of this loss.
Herath
N I
NI
Conjoint Gastroenterology Laboratory, Clinical Research Centre, Royal Brisbane Hospital Research Foundation, Brisbane, Australia.
Kew
M C
MC
Whitehall
V L
VL
Walsh
M D
MD
Jass
J R
JR
Khanna
K K
KK
Young
J
J
Powell
L W
LW
Leggett
B A
BA
Macdonald
G A
GA
D000328:Adult; D000368:Aged; D001315:Australia / Q000208:ethnology; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013019:South Africa / Q000208:ethnology; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins