Adenoviral-mediated pHyde genetransfer and cisplatin additively inhibit human prostate cancer growth by enhancing apoptosis

Yi Lu, Xiongwen Zhang, Ben Beheshti, Jun Zhang

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. 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.METHODS. 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. RESULTS. 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.CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)234-248
Number of pages15
JournalProstate
Volume69
Issue number3
DOIs
StatePublished - Feb 15 2009

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Cisplatin
docetaxel
Prostatic Neoplasms
Apoptosis
Human Chromosomes
Growth
Databases
Genes
Drug Therapy
Neoplasm Genes
Protein Sequence Analysis
Gene Library
Genetic Therapy
In Situ Hybridization
Blood Proteins
Membrane Proteins
Cell Membrane
DNA
In Vitro Techniques
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

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Adenoviral-mediated pHyde genetransfer and cisplatin additively inhibit human prostate cancer growth by enhancing apoptosis. / Lu, Yi; Zhang, Xiongwen; Beheshti, Ben; Zhang, Jun.

In: Prostate, Vol. 69, No. 3, 15.02.2009, p. 234-248.

Research output: Contribution to journalArticle

Lu, Yi ; Zhang, Xiongwen ; Beheshti, Ben ; Zhang, Jun. / Adenoviral-mediated pHyde genetransfer and cisplatin additively inhibit human prostate cancer growth by enhancing apoptosis. In: Prostate. 2009 ; Vol. 69, No. 3. pp. 234-248.
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abstract = "BACKGROUND. 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.METHODS. 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. RESULTS. 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.CONCLUSIONS. 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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