| Summary: | 碩士 === 元培科學技術學院 === 生物技術研究所 === 95 === Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies and is the most lethal of the common urologic cancers in 2006. In adults, RCC accounts for over 85% of all diagnosed renal cancers. The clear cell RCC (ccRCC) is major type in renal cancer. It is high resistance to radiotherapy, immunotherapy and chemotherapy. Surgery remains the most effective method of treating renal cancer. Therefore, to investigate whether tumor associated genes are very important for the molecular mechanisms of RCC, full-length cDNA library of ccRCC and normal kidney constructed by Mr. Sai-Wen Tang was investigated. In the cDNA library, Heme oxygenase 1 (HO-1) and vascular endothelial growth factor A (VEGF-A) were found to be up-reglulated in ccRCC tissues compared to their adjacent normal tissues by real-time polymerase chain reaction.
HO-1 is a heat shock protein and can be induced by various stresses, such as heavy metals, ultraviolet radiation, oxidative stress and inflammation. HO-1 is the rate-limiting enzyme in the degradation of heme into carbon monoxide (CO), iron (Fe2+) and biliverdin. Overexpression of HO-1 is upregulated VEGF-A RNA and protein level in HEK293 cell line. Stable expression of HO-1 is promoted cells migration by wound healing and transwell assay. Using HUVEC tranwell assay it was confirmed that the HO-1 stable clone secreted VEGF-A in the medium to promote HUVEC cells migration. In signal transduction pathways, we found that expression of HO-1 increased the phosphorylation of AKT and ERK 1/2. In nucleus fractionation, HO-1 activated the NFκB expression. By cell viability assay, HO-1 can protect cells which were treated with adriamycin. These results showed that HO-1 expressed was upregulated VEGF-A secretion. Taken together, HO-1 could play a role in the progression of RCC carcinogenesis and promote angiogenesis via VEGF-A secretion.
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