Breast cancer selective gene expression and therapy mediated by recombinant adenoviruses containing the DF3/MUC1 promoter

被引：126

作者：

Chen, L ^{[1
]}

Chen, DS ^{[1
]}

Manome, Y ^{[1
]}

Dong, YH ^{[1
]}

Fine, HA ^{[1
]}

Kufe, DW ^{[1
]}

机构：

[1] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115

来源：

JOURNAL OF CLINICAL INVESTIGATION | 1995年 / 96卷 / 06期

关键词：

adenovirus; breast cancer; thymidine; kinase; beta-galactosidase; gene therapy;

D O I：

10.1172/JCI118347

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The high molecular weight mucin-like glycoprotein, DF3 (MUC1), is overexpressed in the majority of human breast cancers, Here we demonstrate that replication defective recombinant adenoviral vectors, containing the DF3 promoter (bp -725 to +31), can be used to express beta-galactosidase (Ad.DF3-beta gal) and the herpes simplex virus thymidine kinase (HSV-tk) gene (Ad.DFS-tk) in DF3 positive breast carcinoma cell lines, In vivo experiments using breast tumor implants in nude mice injected with Ad.DF3-beta gal demonstrated that expression of the beta-galactosidase gene is limited to DF3-positive breast cancer xenografts, Moreover, in an intraperitoneal breast cancer metastases model, we show that i.p. injection of Ad.DF3-tk followed by GCV treatment results in inhibition of tumor growth, These results demonstrate that utilization of the DF3 promoter in an adenoviral vector can confer selective expression of heterologous genes in breast cancer cells in vitro and in vivo.

引用

页码：2775 / 2782

页数：8

共 43 条

[11] EZZEDDINE ZD, 1991, NEW BIOL, V3, P608
[12] Ginsberg HS, 1984, ADENOVIRUSES
[13] GRAHAM F, 1991, METHODS MOL BIOL GEN
[14] CHARACTERISTICS OF A HUMAN CELL LINE TRANSFORMED BY DNA FROM HUMAN ADENOVIRUS TYPE-5
GRAHAM, FL
SMILEY, J
RUSSELL, WC
NAIRN, R
[J]. JOURNAL OF GENERAL VIROLOGY, 1977, 36 (JUL) : 59 - 72
[15] 2 SYNGENEIC CELL LINES FROM HUMAN BREAST-TISSUE - ANEUPLOID MAMMARY EPITHELIAL (HS578T) AND DIPLOID MYOEPITHELIAL (HS578BST) CELL LINES
HACKETT, AJ
SMITH, HS
SPRINGER, EL
OWENS, RB
NELSONREES, WA
RIGGS, JL
GARDNER, MB
[J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1977, 58 (06) : 1795 - 1806
[16] CHARACTERIZATION OF AN ADENOVIRUS TYPE-5 MUTANT CARRYING EMBEDDED INVERTED TERMINAL REPEATS
HAJAHMAD, Y
GRAHAM, FL
[J]. VIROLOGY, 1986, 153 (01) : 22 - 34
[17] HARRIS JD, 1994, GENE THER, V1, P170
[18] ADENOVIRUS-MEDIATED TRANSFER OF LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE ACUTELY ACCELERATES CHOLESTEROL CLEARANCE IN NORMAL MICE
HERZ, J
GERARD, RD
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) : 2812 - 2816
[19] HORWITZ MS, 1990, VIROLOGY
[20] HUARD J, 1995, GENE THER, V2, P107

← 1 2 3 4 5 →