Abnormal expression of insulin-like growth factor-II and its dynamic quantitative analysis at different stages of hepatocellular carcinoma development.
BACKGROUND
Hepatocellular carcinoma (HCC) is characterized by multiple causes, clear multiple stages and a multifocal process of tumor progression related intimately to the overexpression of many cellular factors. The aim of this study was to investigate the dynamic expression of insulin-like growth factor-II (IGF-II) and its abnormal alteration in the early stages of HCC development.


METHODS
Hepatoma models were induced by 2-fluorenylacetamide (2-FAA) in male Sprague-Dawley rats. Morphological changes of rat livers were assessed by pathological examination (HE staining). The levels of IGF-II expression in the livers and sera of rats were quantitatively detected by an enzyme-linked immunosorbent assay (ELISA). Simultaneously, the expression and cellular distribution of liver IGF-II were analyzed by immunohistochemistry.


RESULTS
Histological examination confirmed that rat hepatocytes showed changes from granule-like degeneration to atypical hyperplasia to HCC, and progressively increasing hepatic IGF-II levels during HCC development. The levels of hepatic or serum IGF-II in HCC tissues and sera were significantly higher than those in normals and rats with degeneration. The immunohistochemical evidence indicated the positive expression and hepatocyte distribution of IGF-II in rat hepatoma. A positive relationship of IGF-II levels was found between liver tissues and sera of experimental rats (P<0.01).


CONCLUSIONS
Hepatic IGF-II may participate in hepatocyte cancer development and detection of IGF-II expression during HCC development could be a useful molecular marker for its early diagnosis.
Qiu
Li-Wei
LW
Research Center of Clinical Molecular Biology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Yao
Deng-Fu
DF
Zong
Lei
L
Lu
Yuan-Yuan
YY
Huang
Hua
H
Wu
Wei
W
Wu
Xin-Hua
XH
D015073:2-Acetylaminofluorene; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D007335:Insulin-Like Growth Factor II; D015073:2-Acetylaminofluorene