TY - JOUR
T1 - Growth inhibition of human cervical cancer cells with the recombinant adenovirus p53 in vitro
AU - Hamada, Katsuyuki
AU - Zhang, Wei Wei
AU - Alemany, Ramon
AU - Wolf, Judith
AU - Roth, Jack A.
AU - Mitchell, Michele Follen
N1 - Funding Information:
1This study was partially supported by grants from the National Cancer Institutes and the National Institute of Health (RO1 CA45187) (J.A.R.); by gifts to the Division of Surgery from Tenneco and Exxon for the Core Laboratory Facility; by the M. D. Anderson Cancer Center Support Core Grant (CA16672); and by a grant from the Mathers Foundation, the University Cancer Foundation, and the Business and Professional Women’s Fund.
PY - 1996/3
Y1 - 1996/3
N2 - Human papillomavirus (HPV) has been identified in the majority of invasive cancers of the uterine cervix sampled and has been found to contribute in a significant way to the genesis of human cervical cancer. HPV has two transforming genes that encode the oncoproteins E6 and E7. E6 can form complexes with p53 and promote p53 degradation. We introduced wild- type p53 into a cervical cancer cell line via a recombinant adenoviral vector, Ad5CMV-p53. Human cervical cancer cell line HeLa, which has HPV type 18 and wild-type p53, was used in this study. Cells were grown in RPMI medium supplemented with 10% heat-inactivated fetal bovine serum. Ad5CMV- p53 was created by inserting the cytomegalovirus promoter, wild-type p53 cDNA, and SV40 polyadenylation signal in a minigene cassette into the E1- deleted region of the modified Ad5 adenovirus. The transduction efficiency was 100% when a dose ensuring a multiplicity of infection of 100 or greater was used. The p53 protein was detected in Ad5CMV-p53-infected cells by immunohistochemical and Western blot analyses. The growth of the Ad5CMV- p53-infected cells was greatly suppressed as detected by both cell count and [3H]thymidine incorporation assay. These data suggest that transfection of HPV-positive cervical cancer cells with a wild-type p53 gene in a form such as Ad5CMV-p53 is a potential novel therapy for cervical cancer.
AB - Human papillomavirus (HPV) has been identified in the majority of invasive cancers of the uterine cervix sampled and has been found to contribute in a significant way to the genesis of human cervical cancer. HPV has two transforming genes that encode the oncoproteins E6 and E7. E6 can form complexes with p53 and promote p53 degradation. We introduced wild- type p53 into a cervical cancer cell line via a recombinant adenoviral vector, Ad5CMV-p53. Human cervical cancer cell line HeLa, which has HPV type 18 and wild-type p53, was used in this study. Cells were grown in RPMI medium supplemented with 10% heat-inactivated fetal bovine serum. Ad5CMV- p53 was created by inserting the cytomegalovirus promoter, wild-type p53 cDNA, and SV40 polyadenylation signal in a minigene cassette into the E1- deleted region of the modified Ad5 adenovirus. The transduction efficiency was 100% when a dose ensuring a multiplicity of infection of 100 or greater was used. The p53 protein was detected in Ad5CMV-p53-infected cells by immunohistochemical and Western blot analyses. The growth of the Ad5CMV- p53-infected cells was greatly suppressed as detected by both cell count and [3H]thymidine incorporation assay. These data suggest that transfection of HPV-positive cervical cancer cells with a wild-type p53 gene in a form such as Ad5CMV-p53 is a potential novel therapy for cervical cancer.
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U2 - 10.1006/gyno.1996.0057
DO - 10.1006/gyno.1996.0057
M3 - Article
C2 - 8774641
AN - SCOPUS:0029993623
SN - 0090-8258
VL - 60
SP - 373
EP - 379
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -