Tsang Tsun Yee, Tang Wan Yee, Tsang Wing Pui, Co Ngai Na, Kong Siu Kai, Kwok Tim Tak
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Apoptosis. 2008 Sep;13(9):1135-47. doi: 10.1007/s10495-008-0241-6.
Hepatoma-derived growth factor (HDGF) is highly expressed in human cancer and its expression is correlated with poor prognosis of cancer. The growth factor is known to stimulate cell growth while the underlying mechanism is however not clear. Transfection with HDGF cDNA stimulated while its specific antisense oligonucleotides repressed the growth of human hepatocellular carcinoma HepG2 cells. Furthermore, knock-down of HDGF by antisense oligos also induced apoptosis in HepG2 cells and in other human cancer cells, e.g. human squamous carcinoma A431 cells. HDGF knock-down was found to induce the expression of the pro-apoptotic protein Bad and also inactivate ERK and Akt, which in turn led to dephosphorylation of Bad at Ser-112, Ser-136, and activation of the intrinsic apoptotic pathway, i.e. depolarization of the mitochondrial membrane, release of mitochondrial cytochrome c, increase in the processing of caspase 9 and 3. As HDGF knock-down not only suppresses the growth but also induces apoptosis in human cancer cells, HDGF may therefore serve as a survival factor for human cancer cells and a potential target for cancer therapy.
肝癌衍生生长因子（HDGF）在人类癌症中高表达，其表达与癌症预后不良相关。已知该生长因子可刺激细胞生长，但其潜在机制尚不清楚。用HDGF cDNA转染可刺激人肝癌HepG2细胞生长，而其特异性反义寡核苷酸则抑制该细胞生长。此外，反义寡核苷酸敲低HDGF也可诱导HepG2细胞以及其他人类癌细胞（如人鳞状细胞癌A431细胞）凋亡。研究发现，敲低HDGF可诱导促凋亡蛋白Bad的表达，还可使ERK和Akt失活，进而导致Bad在Ser-112、Ser-136位点去磷酸化，并激活内源性凋亡途径，即线粒体膜去极化、线粒体细胞色素c释放、半胱天冬酶9和3的加工增加。由于敲低HDGF不仅能抑制人类癌细胞生长，还能诱导其凋亡，因此HDGF可能是人类癌细胞的存活因子及癌症治疗的潜在靶点。
