Adenoviral-mediated pHyde gene transfer and cisplatin additively inhibit human prostate cancer growth by enhancing apoptosis.

Adenoviral-mediated pHyde gene transfer and cisplatin additively inhibit human prostate cancer growth by enhancing apoptosis.
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DOI:
10.1002/pros.20867
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发表时间:
2009-02-15
期刊:
影响因子:
2.8
通讯作者:
Zhang, Jun
Zhang, Jun
中科院分区:
医学3区
文献类型:
--
作者:
Lu, Yi;Zhang, Xiongwen;Beheshti, Ben;Zhang, Jun

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我们最近克隆了一个新的基因——大鼠pHyde。同一研究小组显示,大鼠pHyde通过诱导细胞凋亡对人类前列腺癌具有生长抑制作用。在本报告中,通过cDNA文库筛选克隆了人类同源物,即大鼠pHyde的hpHyde。通过数据库检索和原位杂交,对人类染色体中hpHyde的基因组位点进行了定位。使用表达 pHyde 的腺病毒载体 (AdRSVpHyde) 分别与 DNA 损伤化疗剂、顺铂和多西紫杉醇组合,通过体外和体内测定分析 pHyde 与化疗药物联合的抗前列腺癌作用。数据库搜索和FISH分析一致表明hpHyde基因定位于人类染色体2q14。蛋白质序列分析表明 hpHyde 可能是质膜蛋白。 hpHyde 在人体各种正常组织和器官中存在差异表达,提示 hpHyde 可能在发育和分化中发挥作用。在体外和体内,用 AdRSVpHyde 和顺铂处理的 DU145 人前列腺癌细胞的生长抑制和细胞凋亡诱导均比单独使用任一药物更强。此外,AdRSVpHyde和多西紫杉醇对DU145细胞生长也具有类似的叠加抑制作用。一个新的基因 hpHyde(大鼠 pHyde 的人类同源物)已被克隆,并且已确定其在人类染色体中的基因组位置。我们的结果支持 pHyde 可能用于前列腺癌基因治疗并结合化疗以提高治疗指数。
A novel gene, rat pHyde, has been cloned by us recently. The rat pHyde was shown by the same group to have growth inhibitory effects on human prostate cancer through the induction of apoptosis. In this report, a human homologue, hpHyde of the rat pHyde, was cloned by cDNA libraries screening. The database search and in situ hybridization were used to map the genomic loci of hpHyde in human chromosome. The anti-prostate cancer effects of pHyde in conjunction with chemotherapy agent were analyzed by in vitro and in vivo assays using adenoviral vector expressing pHyde (AdRSVpHyde) in combination with DNA damaging chemotherapeutic agent, cisplatin, and docetaxel, respectively. Database search and FISH analysis consistently indicated that hpHyde gene localizes at human chromosome 2q14. Protein sequence analysis suggests that hpHyde may be a plasma membrane protein. hpHyde is differentially expressed in various normal human tissues and organs, suggesting that hpHyde may play roles in development and differentiation. Growth suppression and induction of apoptosis were additively greater in DU145 human prostate cancer cells treated with AdRSVpHyde and cisplatin than either agent alone both in vitro and in vivo. Moreover, AdRSVpHyde and docetaxel also have a similar additively inhibitory effect on DU145 cell growth. A novel gene hpHyde, the human homologue of rat pHyde, has been cloned and its genomic location in the human chromosome has been identified. Our results support the potential use of pHyde for prostate cancer gene therapy coupled with chemotherapy to improve therapeutic index.
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