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J.
Cancer Mol. 4: 91-96, 2008
[Research Paper]
Abnormal Expression of Hepatic Transforming Growth Factor-beta1 at the
Early Stage of Hepatocellular Carcinoma Formation
Zhizhen
Dong, Dengfu Yao, Yilang Wang, Junjun Shen, Chongguo Zhang, Hua Huang,
Liwei Qiu, Wei Wu, and Xinhua Wu
Department of Diagnostics, Medical College of
Nantong University, Nantong, Jiangsu Province, China [Z. Dong]; Research
Center of Clinical Molecular Biology [Z. Dong, D. Yao, L. Qiu, W. Wu, X.
Wu], Center of Oncology [Y. Wang, J. Shen, C. Zhang],
and
Department of Pathology [H. Huang], Affiliated Hospital of Nantong
University, Nantong, Jiangsu Province, China
Abstract:
AIM:
The study was aimed to investigate the dynamic alteration of hepatic
transforming growth factor (TGF)-beta1 expression during the formation
of hepatocellular carcinoma.
METHODS:
The animal model for hepatocarcinogenesis was made with male Sprague-Dawley
(SD) rats induced with
0.05% of 2-fluorenylacetamide.
Morphological changes in rat livers were examined by Hematoxylin and
Eosin staining. Hepatic total RNA was extracted from rat livers and
TGF-beta1 mRNA level was analyzed by nested RT-PCR. The levels of
TGF-beta1 in liver and blood were quantitatively detected by ELISA.
Simultaneously, hepatocyte distribution of TGF-beta1 was analyzed by
immunohistochemistry.
RESULTS:
Our histopathological data confirmed the
2-fluorenylacetamide-induced
malignant transformation of rat hepatocytes progressed from granule-like
degeneration to atypical hyperplasia to hepatoma formation. The
expression levels of rat hepatic total RNA, TGF-beta1 mRNA, and
TGF-beta1 protein were significantly increased with the
histopathological changes. They were significantly higher in cancerous
group than those in any group of control, hepatocyte degeneration, and
precancerous lesion (P < 0.05). An increasing trend of hepatic
TGF-beta1 protein was in accordance with TGF-beta1 mRNA, especially in
precancerous or cancerous tissues, and a closely positive relationship
was found between the levels of hepatic and circulating TGF-beta1
protein.
CONCLUSION:
Our data support that TGF-beta1 participates in hepatocarcinogenesis,
and its abnormal expression is associated with malignant transformation
of hepatocytes.
(Keywords: HCC;
TGF-beta1; dynamic expression; hepatocarcinogenesis)
Received
5/26/08;
Revised 6/24/08;
Accepted 6/26/08.
1Correspondence:
Dr.
Dengfu Yao, Research
Center of Clinical Molecular Biology, Affiliated Hospital of Nantong
University,
Nantong,
Jiangsu Province 226001, China. Phone:
86-513-85052413. Fax: 86-513-85052523.
E-mail:
yaodf@ahnmc.com
2Abbreviations:
TGF-beta1,
transforming growth factor-beta1; HCC, hepatocellular carcinoma; AFP,
alpha-fetoprotein; SD, Sprague-Dawley; 2-FAA,
2-fluorenylacetamide.
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