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由含DF3/MUC1启动子的重组腺病毒介导的乳腺癌选择性基因表达与治疗

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

作者信息

Chen L, Chen D, Manome Y, Dong Y, Fine H A, Kufe D W

机构信息

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

J Clin Invest. 1995 Dec;96(6):2775-82. doi: 10.1172/JCI118347.

DOI:10.1172/JCI118347
PMID:8675647
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC185987/
Abstract

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-betagal) and the herpes simplex virus thymidine kinase (HSV-tk) gene (Ad.Df3-tk) in DF3 positive breast carcinoma cell lines. In vivo experiments using breast tumor implants in nude mice injected with Ad.DF3-betagal 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.

摘要

高分子量粘蛋白样糖蛋白DF3（MUC1）在大多数人类乳腺癌中过度表达。在此我们证明，含有DF3启动子（碱基对-725至+31）的复制缺陷型重组腺病毒载体可用于在DF3阳性乳腺癌细胞系中表达β-半乳糖苷酶（Ad.DF3- betagal）和单纯疱疹病毒胸苷激酶（HSV-tk）基因（Ad.Df3-tk）。在裸鼠体内使用乳腺肿瘤植入物并注射Ad.DF3- betagal的实验表明，β-半乳糖苷酶基因的表达仅限于DF3阳性乳腺癌异种移植物。此外，在腹膜内乳腺癌转移模型中，我们发现腹腔注射Ad.DF3-tk后再进行GCV治疗可抑制肿瘤生长。这些结果表明，在腺病毒载体中利用DF3启动子可在体外和体内赋予乳腺癌细胞中异源基因的选择性表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/b3953bca7229/jcinvest00018-0246-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/d2da49572afa/jcinvest00018-0242-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/947817b4c2d4/jcinvest00018-0242-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/62be0adb0d18/jcinvest00018-0242-f.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/b57d952f6db9/jcinvest00018-0242-g.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/b3245c8c5204/jcinvest00018-0242-h.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/fa585eaeb497/jcinvest00018-0242-i.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/7902afb0dfc9/jcinvest00018-0244-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/05434ffbcdb4/jcinvest00018-0245-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/b3953bca7229/jcinvest00018-0246-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/d2da49572afa/jcinvest00018-0242-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/1891ed9a9ba8/jcinvest00018-0242-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/461b11ea057d/jcinvest00018-0242-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/6ba2694fb377/jcinvest00018-0242-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/947817b4c2d4/jcinvest00018-0242-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/62be0adb0d18/jcinvest00018-0242-f.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/b57d952f6db9/jcinvest00018-0242-g.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/b3245c8c5204/jcinvest00018-0242-h.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/fa585eaeb497/jcinvest00018-0242-i.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/7902afb0dfc9/jcinvest00018-0244-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/05434ffbcdb4/jcinvest00018-0245-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d36/185987/b3953bca7229/jcinvest00018-0246-a.jpg

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