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Research article

Construction of an MUC-1 promoter driven, conditionally

replicating adenovirus that expresses the sodium iodide

symporter for gene therapy of breast cancer

Miguel A Trujillo1, Michael J Oneal2, Julia Davydova3, Elizabeth Bergert1, Masato Yamamoto3 and

John C Morris III1

Abstract

Introduction The sodium iodide symporter (NIS) directs the

uptake and concentration of iodide in thyroid cells. This in turn

allows radioiodine imaging and therapy for thyroid cancer. To

extend the use of NIS-mediated radioiodine therapy to other

types of cancer, we successfully transferred and expressed the

sodium-iodide symporter (NIS) gene in prostate, colon, and

breast cancer cells both in vivo and in vitro by using nonreplicating

adenoviral vectors.

Methods To improve virotherapy efficiency, we developed a

conditionally replicating adenovirus (CRAd) in which the

transcriptional cassette RSV promoter-human NIScDNA-bGH

polyA was also inserted at the E3 region. The E1a gene is driven

by the tumor-specific promoter MUC-1 in the CRAd

Ad5AMUCH_RSV-NIS.

Results In vitro infection of the MUC-1-positive breast cell line

T47D resulted in virus replication, cytolysis, and release of

infective viral particles. Conversely, the MUC-1-negative breast

cancer cell line MDA-MB-231 was refractory to the viral

cytopathic effect and did not support viral replication. The data

indicate that Ad5AMUCH_RSV-NIS activity is stringently

restricted to MUC-1-positive cancer cells. Radioiodine uptake

was readily measurable in T47 cells infected with

Ad5AMUCH_RSV-NIS 24 hours after infection, thus confirming

NIS expression before viral-induced cell death.

Conclusions This construct may allow multimodal therapy,

combining virotherapy with radioiodine therapy to be developed

as a novel treatment for breast and other MUC1-overexpressing

cancers.

1 個解答

評分
  • 1 0 年前
    最佳解答

    答案:

    研究文章

    被驅使的 MUC-1 促進者的工程,有條件地

    複製表達鈉碘化物的腺病毒

    symporter 為乳癌的基因治療

    Miguel Trujillo1 、麥可 J Oneal 2 、茱莉亞 Davydova3 、伊莉莎白 Bergert 1, Masato Yamamoto3 和

    約翰 C 莫理斯 31

    摘要

    介紹鈉碘化物 symporter(NIS)指示那

    在甲狀腺的細胞中的舉起和碘化物的集中。 這依次

    對於甲狀腺的癌症允許描繪的 radioiodine 和治療。 到

    exte

    我發誓保證對=ˇ=

    2009-10-14 21:02:55 補充:

    我發誓保證對=ˇ=

    這個不是裡面的喔=ˇ=

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