The Inhibition and Mechanism of Programmed Cell Death 10 (PDCD10) on Brain Cancer Cell Metastasis

• Main Authors: Tz-Wei Lin, 林子為
• Other Authors: Yiu-Kay Lai
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/84165982314568029026

碩士 === 國立清華大學 === 生物科技研究所 === 95 === Programmed cell death 10 (PDCD10, TFAR15) is a member of the PDCD family associated with cell apoptosis. It was originally identified in the human premyeloid TF-1 cells for being up-regulated, in which apoptosis was induced by withdrawal of granulocyte macrophage colony-stimulating factor (GM-CSF). Clinical statistics have shown that mutations of PDCD10 are correlated with cerebral cavernous malformation (CCM) and thus this gene is also named as CCM3 (cerebral cavernous malformation 3) accordingly. The expression of PDCD10 was reported to be up-regulated in human promyeloblast HL-60 cells after serum starvation. The elevated PDCD10 then modulates the ERK (extracellular signal-regulated kinase) signaling pathway to promote cell growth and cellular transformation. Surprisingly, in this thesis it is found that the PDCD10 expression is in fact down-regulated in serum-free culture condition. By using the purified PDCD10 recombinant protein as an antigen, I successfully generated mouse anti-human PDCD10 polyclonal antibody. With this new antibody, I was able to further clarify that the PDCD10 protein expression is down-regulated in HL-60 cells after serum starvation. Meanwhile, overexpression of PDCD10 not only significantly suppresses the invasive ability of human glioblastoma U-87 MG cells, but also increases the expression and secretion of MMP9 as well as the ERK activity. Treatment of mitogen-activated protein kinase kinase (MAPKK) inhibitor PD98059 resulted in a suppression of the ERK activity and subsequent decrease of the MMP9 expression. Together these results suggest that PDCD10 may be an anti-apoptotic gene which affects cell apoptotic process as well as tumor cell invasion and metastasis by regulating the expression of MMP9 via the ERK pathway.