The Cellular Effects of SERPINB13 in Prostate Cancer Cells.

• Main Authors: Cheng-Hung Lu, 呂政鴻
• Other Authors: Ban-Dar Hsu
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/s6z479

碩士 === 國立清華大學 === 生物技術研究所 === 92 === The incidence rate and death rate of prostate cancer have been rapidly increasing in the past 10 years in Taiwan. It has became the eighth most common cause of cancer-related death. The survival rate for patients diagnosed with prostate cancer at early stage is 90%. As it happens to metastasis, the survival rate drops to 30%. Preventing and inhibiting the further invasion and metastasis of prostate cancer will raise the survival rate for patients who suffer from prostate cancer. Bone is second most common site of metastasis (after lymph nodes) for the prostate cancer. Lesions associated with prostate cancer generally exhibit increased bone formation and resorption. Increased bone resportion may release factors from the extracellular matrix that contribute to tumor growth. Cathepsin K is a protease that exhibits strong degradative activity against the extracellular matrix. It is the target protease of SERPINB13. Serine proteinase inhibitor SERPINB13 has been grouped into the cluster of clade B serpins located at chromosome 18q21.3. SERPINB5 was a tumor suppressor gene in the same cluster This region is a known area for lost of heterozygosity (LOH) and associated with many malignancies. On the basis of this reason, SERPINB13 may represent an equivalent gene to SERPINB5 in prostate cancer. SERPINB13 gene has three different splicing forms. They show altered lengths of the part of exon 3 that forms interhelical loop, According to the decreasing of the interhelical loop,we call them SERPINB13(0), SERPINB13(-9) and SERPINB13(-10). To know the role of SERPINB13 in prostate cancer, we examined the SERPINB13 expression in prostate cell lines by RT-PCR. The expression pattern illustrates SERPINB13 downregulation in prostate cancer . Then screen a more invasive prostate cancer cell line PC-3 as our candidate cell line by in vitro invasion assay. Three constructed plasmids with different splicing forms were transfected into PC-3 cells. First of all, the western blot confirmed the expression of SERPINB13 and the growth rate of PC-3 cells was not changed by transfection in the cell proliferation test. In the in vitro invasion assay of SERPINB13 transfected PC-3 cells, PC-3 cells overexpress SERPINB13 were more invasive than vector alone. The ability of invasion was decreasing as the increasing of the interhelical loop. The results show prostate cancer overexpresses SERPINB13 will increase invasion and metastasis ability. It can be proven to be related to prostate cancer. Understanding the detailed mechanism of SERPINB13 remains an ongoing challenge. But it can provide us a new aspect in protecting prostate cancer metastasis.