Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence

Mitchell S. Steiner, Yu Zhang, Farees Farooq, Jody Lerner, Ying Wang, Yi Lu

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

It is estimated that there will be >184,500 new cases of prostate cancer and 42,000 prostate cancer deaths in the United States this year. In the majority of patients diagnosed with prostate cancer, the disease will be too advanced for cure with standard medical treatment. New therapeutic strategies against advanced prostate cancer are desperately needed. As alterations in tumor-suppressor gene p16 are common in prostate cancer, one novel approach is gene therapy using a replication-deficient, E1/E3-deleted adenovirus type 5 containing a p16 under the control of a truncated Rous sarcoma virus promoter (AdRSVp16). In vitro, PC-3 cells that had been stably transfected with p16 expression vector under the control of an inducible promoter had a 70% reduction in cell number compared with the parental and control vector- transfected PC-3 cells. Similarly, AdRSVp16 significantly inhibited the growth of PPC-1 and PC-3 prostate cancer cells in culture. Furthermore, PPC-1 tumors grown in nude mice treated by a single injection of AdRSVp16 had a marked reduction in tumor size compared with untreated control-treated or vital control-treated PPC-1 tumors. Animals bearing tumors treated with AdRSVp16 also had longer survival. Adenovirally mediated expression of transgene was detected in xenograft tumors for at least 2 weeks. Taken together, these results suggest that AdRSVp16 should be considered for prostate cancer gene therapy in human clinical trials.

Original languageEnglish (US)
Pages (from-to)360-372
Number of pages13
JournalCancer Gene Therapy
Volume7
Issue number3
DOIs
StatePublished - Jan 1 2000

Fingerprint

Cell Aging
Prostatic Neoplasms
Survival
Growth
Neoplasms
Genetic Therapy
Rous sarcoma virus
Neoplasm Genes
Tumor Suppressor Genes
Transgenes
Heterografts
Adenoviridae
Nude Mice
Cell Culture Techniques
Cell Count
Clinical Trials
Injections
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence. / Steiner, Mitchell S.; Zhang, Yu; Farooq, Farees; Lerner, Jody; Wang, Ying; Lu, Yi.

In: Cancer Gene Therapy, Vol. 7, No. 3, 01.01.2000, p. 360-372.

Research output: Contribution to journalArticle

Steiner, Mitchell S. ; Zhang, Yu ; Farooq, Farees ; Lerner, Jody ; Wang, Ying ; Lu, Yi. / Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence. In: Cancer Gene Therapy. 2000 ; Vol. 7, No. 3. pp. 360-372.
@article{3742cbf7b1004e1785210e3c01f5ea19,
title = "Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence",
abstract = "It is estimated that there will be >184,500 new cases of prostate cancer and 42,000 prostate cancer deaths in the United States this year. In the majority of patients diagnosed with prostate cancer, the disease will be too advanced for cure with standard medical treatment. New therapeutic strategies against advanced prostate cancer are desperately needed. As alterations in tumor-suppressor gene p16 are common in prostate cancer, one novel approach is gene therapy using a replication-deficient, E1/E3-deleted adenovirus type 5 containing a p16 under the control of a truncated Rous sarcoma virus promoter (AdRSVp16). In vitro, PC-3 cells that had been stably transfected with p16 expression vector under the control of an inducible promoter had a 70{\%} reduction in cell number compared with the parental and control vector- transfected PC-3 cells. Similarly, AdRSVp16 significantly inhibited the growth of PPC-1 and PC-3 prostate cancer cells in culture. Furthermore, PPC-1 tumors grown in nude mice treated by a single injection of AdRSVp16 had a marked reduction in tumor size compared with untreated control-treated or vital control-treated PPC-1 tumors. Animals bearing tumors treated with AdRSVp16 also had longer survival. Adenovirally mediated expression of transgene was detected in xenograft tumors for at least 2 weeks. Taken together, these results suggest that AdRSVp16 should be considered for prostate cancer gene therapy in human clinical trials.",
author = "Steiner, {Mitchell S.} and Yu Zhang and Farees Farooq and Jody Lerner and Ying Wang and Yi Lu",
year = "2000",
month = "1",
day = "1",
doi = "10.1038/sj.cgt.7700151",
language = "English (US)",
volume = "7",
pages = "360--372",
journal = "Cancer Gene Therapy",
issn = "0929-1903",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence

AU - Steiner, Mitchell S.

AU - Zhang, Yu

AU - Farooq, Farees

AU - Lerner, Jody

AU - Wang, Ying

AU - Lu, Yi

PY - 2000/1/1

Y1 - 2000/1/1

N2 - It is estimated that there will be >184,500 new cases of prostate cancer and 42,000 prostate cancer deaths in the United States this year. In the majority of patients diagnosed with prostate cancer, the disease will be too advanced for cure with standard medical treatment. New therapeutic strategies against advanced prostate cancer are desperately needed. As alterations in tumor-suppressor gene p16 are common in prostate cancer, one novel approach is gene therapy using a replication-deficient, E1/E3-deleted adenovirus type 5 containing a p16 under the control of a truncated Rous sarcoma virus promoter (AdRSVp16). In vitro, PC-3 cells that had been stably transfected with p16 expression vector under the control of an inducible promoter had a 70% reduction in cell number compared with the parental and control vector- transfected PC-3 cells. Similarly, AdRSVp16 significantly inhibited the growth of PPC-1 and PC-3 prostate cancer cells in culture. Furthermore, PPC-1 tumors grown in nude mice treated by a single injection of AdRSVp16 had a marked reduction in tumor size compared with untreated control-treated or vital control-treated PPC-1 tumors. Animals bearing tumors treated with AdRSVp16 also had longer survival. Adenovirally mediated expression of transgene was detected in xenograft tumors for at least 2 weeks. Taken together, these results suggest that AdRSVp16 should be considered for prostate cancer gene therapy in human clinical trials.

AB - It is estimated that there will be >184,500 new cases of prostate cancer and 42,000 prostate cancer deaths in the United States this year. In the majority of patients diagnosed with prostate cancer, the disease will be too advanced for cure with standard medical treatment. New therapeutic strategies against advanced prostate cancer are desperately needed. As alterations in tumor-suppressor gene p16 are common in prostate cancer, one novel approach is gene therapy using a replication-deficient, E1/E3-deleted adenovirus type 5 containing a p16 under the control of a truncated Rous sarcoma virus promoter (AdRSVp16). In vitro, PC-3 cells that had been stably transfected with p16 expression vector under the control of an inducible promoter had a 70% reduction in cell number compared with the parental and control vector- transfected PC-3 cells. Similarly, AdRSVp16 significantly inhibited the growth of PPC-1 and PC-3 prostate cancer cells in culture. Furthermore, PPC-1 tumors grown in nude mice treated by a single injection of AdRSVp16 had a marked reduction in tumor size compared with untreated control-treated or vital control-treated PPC-1 tumors. Animals bearing tumors treated with AdRSVp16 also had longer survival. Adenovirally mediated expression of transgene was detected in xenograft tumors for at least 2 weeks. Taken together, these results suggest that AdRSVp16 should be considered for prostate cancer gene therapy in human clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=0034115639&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034115639&partnerID=8YFLogxK

U2 - 10.1038/sj.cgt.7700151

DO - 10.1038/sj.cgt.7700151

M3 - Article

VL - 7

SP - 360

EP - 372

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

SN - 0929-1903

IS - 3

ER -