Role of pHyde novel gene product as an intrinsic factor for apoptotic pathway in prostate cancer.
Role of pHyde novel gene product as an intrinsic factor for apoptotic pathway in prostate cancer.
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发表时间：
2000-05
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通讯作者：
A. Rinaldy;R. Menon;J. Lerner;M. Steiner
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作者：
A. Rinaldy;R. Menon;J. Lerner;M. Steiner
诱导细胞凋亡的机制可由内在因素(S)调控，如直接上调细胞凋亡途径的基因产物(S)，或通过下调抗凋亡基因间接调控。在被癌症干扰的生物系统中，这种动态平衡是一种正常现象。因此，寻找在癌症基因治疗中可能具有潜在应用的、作为细胞凋亡途径上调因子的基因是很重要的。我们克隆了一种新的大鼠基因，命名为pHyde，实现了这一目标。在内部，这种pHyde基因产物使稳定转基因的大鼠前列腺癌细胞系即使在没有任何外部诱导剂的情况下也更容易发生凋亡。在外源药物如5-氟-2‘-脱氧尿苷(FdUr)的作用下，稳定的转染体的细胞凋亡反应更高，提示内因和外因协同作用。PHyde基因产物被称为内源性因子，而FdUr被认为是导致大鼠前列腺癌模型细胞凋亡的外源性因子。
Induction of apoptotic cell death mechanism can be regulated by internal factor(s), such as by gene product(s) that directly upregulate the apoptosis pathway or indirectly by down-regulating the anti-apoptosis gene. This homeostasis is a normal phenomenon in a biological system disturbed by cancer. It is thus important to find any gene functioning as an upregulator for the apoptosis pathway that may have a potential application in the context of cancer gene therapy. We have cloned a novel rat gene, denoted as pHyde, that fulfilled this objective. Internally, this pHyde gene product renders the stable transfectant of rat prostatic cancer cell lines more susceptible to apoptosis even without any external inducer. By using an external agent, such as 5-fluoro-2'-deoxyuridine (FdUr), apoptotic responses of the stable transfectants are even higher, suggesting that both intrinsic and extrinsic factors work synergistically. The pHyde gene product was termed an intrinsic factor, whereas FdUr was considered an extrinsic factor for the apoptosis in rat prostate cancer model.