Hepatocellular carcinoma (HCC) is the most common and devastating malignant tumor in Taiwan. The major factors involved in the molecular pathogenesis for the development of HCC have been explored in recent years. An extensive array of growth factors and their receptors have been identified and may act as positive and negative modulators in different stages of hepatocarcinogenesis. HDGF (hepatoma-derived growth factor) is a novel growth factor, identified from conditioned medium of hepatoma cell line. HDGF has growth stimulating activity for fibroblast and some hepatoma cells. The high homology of protein sequence to HMG (high mobility group) protein but with distinct structure indicate it is a novel growth factor with mitogenic effect. Recently, elevated HDGF expression was found in developing kidneys but little in adult kidney. Besides, HDGF expression was found to be correlated with angiogenic status of tissues. Thus, it is speculated that HDGF plays a role during embryonic development and angiogenesis. Besides, HDGF also plays a role in cell-to-cell interaction and cell movement. HDGF is a growth factor that is involved in stimulating vascular smooth muscle cells (SMCs) proliferation during development and in disease. HDGF contains a true bipartite nuclear localization sequence necessary for nuclear targeting. It is required for HDGF stimulation of DNA replication and cell proliferation in vascular smooth muscle cell. In present studies, have transfected HDGF cDNA to 3T3 cell and the HDGF expression was verified by Western blot analysis. HDGF expression altered the morphologies and growth rate of 3T3 cells by 2-fold. Besides, HDGF-expressing cells were more resistant to serum-starvation. Injection of 3T3-HDGF cells, but not 3T3 cells, resulted in tumor formation in nude mice, suggesting that the angiogenic and mitogenic functions of HDGF might contribute to carcinogenesis. By using various reagents including H2O2, dexamethasome, taxol, cisplatin, CoCl2 and KCN, the cellular stress studies revealed differential responses between in 3T3 and 3T3-HDGFH. analyzed dose and time-dependent effects of UV irradiation and found that 3T3-HDGF cells are more sensitive to UV irradiation than 3T3 cells and susceptible to apoptosis. hope these experiments will bring further insights into the cellular function of HDGF, particularly during angiogenic process, thereby enable to evaluate its role during HCC progression and its potential as clinical marker and therapeutic target for HCC.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0628102-011822 |
| Date | 28 June 2002 |
| Creators | Ma, Yi-Ling |
| Contributors | Ming-Hong Tai, Ching-Mei Hsu, Jiin-Tsuey Cheng |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0628102-011822 |
| Rights | campus_withheld, Copyright information available at source archive |
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