Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis

Citation
Ml. Lu et al., Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis, AM J PATH, 159(3), 2001, pp. 945-953
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
0002-9440 → ACNP
Volume
159
Issue
3
Year of publication
2001
Pages
945 - 953
Database
ISI
SICI code
0002-9440(200109)159:3<945:AEOFRP>2.0.ZU;2-6
Abstract
p62 is a RNA-binding protein that was isolated by immunoscreening a cDNA ex pression library with autoantibodies from patients with hepatocellular carc inoma (HCC). This autoantigen binds to mRNA encoding insulin-like growth fa ctor II, which has been found to be overexpressed in HCC and is tumorigenic in transgenic animals. Immunohistochemical analysis of HCC liver showed th at 33% (9 of 27) exhibited readily detectable staining of p62 protein in th e cytoplasm of all malignant cells in cancer nodules, whereas it was undete ctable in adjacent nonmalignant liver cells. In addition one of two patient s with cholangiocarcinoma expressed p62 in malignant bile duct epithelial c ells. p62 expression was also detected in scattered cells in cirrhotic nodu les in contrast to uniform expression in all cells in HCC nodules. In HCC n odules, p62 mRNA was also detected by reverse transcriptase-polymerase chai n reaction analysis. Nine normal adult livers did not contain detectable p6 2 mRNA or p62 protein whereas five fetal livers were all positive for mRNA and protein. The observations show that p62 is developmentally regulated, e xpressed in fetal, but not in adult liver, and aberrantly expressed in HCC and could be playing a role in abnormal cell proliferation in HCC and cirrh osis by modulating expression of growth factors such as insulin-like growth factor II.