Adenoviral-mediated pHyde gene transfer and cisplatin additively inhibit human prostate cancer growth by enhancing apoptosis.
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.
Lu
Yi
Y
Department of Pathology and Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. ylu@utmem.edu
Zhang
Xiongwen
X
Beheshti
Ben
B
Zhang
Jun
J
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D018076:DNA, Complementary; D000077143:Docetaxel; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D010088:Oxidoreductases; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017385:Sequence Homology; D043823:Taxoids / Q000494:pharmacology
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D015513:Oncogene Proteins; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D010088:Oxidoreductases; C486677:STEAP3 protein, human; D053148:Caspase 3; D002945:Cisplatin