111 336

Cited 0 times in

Tumor-specific Gene Therapy for Renal Cell Carcinoma Using MN/CA9-directed Replication-competent Adenovirus

Other Title
MN/CA9 촉진자를 가진 Replication-competent 아데노바이러스를 이용한 신세포암에 대한 종양 특이적 유전자요법
Authors
김, 세중; 안, 미원; 임, 호영; 정, 현철; Gardner, Thomas A.; Kao, Chinghai; 이, 상진; 최, 민규; 김, 영수
Citation
Taehan Pinyogikwa Hakhoe chi, 45(5):456-462, 2004
Journal Title
Taehan Pinyogikwa Hakhoe chi; The Korean journal of urology; 대한비뇨기과학회지
ISSN
0494-4747
Abstract
Purpose: A new therapeutic approach is needed in patients with metastatic renal cell carcinoma (RCC) because of a dismal prognosis. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 protein is highly expressed in RCC tissues, but not in normal kidney, we constructed a tumor-specific replication-competent adenoviral vector utilizing MN/CA9 promoter (Ad-MN/CA9-E1a) and demonstrated its selective cytotoxicity toward MN/CA9-expressing RCC cells in vitro.



Materials and Methods: MN/CA9-positive (HeLa, SK-RC-52) and MN/ CA9-negative (SK-RC-29) cells were used. RT-PCR assay for MN/CA9 mRNA was performed in each cells. Ad5 E1a protein production in each cells after infection with Ad-MN/CA9-E1a was determined by western blot analysis. In vitro cytotoxicity assay was performed for assessing the selective cytotoxicity of Ad-MN/CA9-E1a to MN/CA9-expressing cells.



Results: RT-PCR assay showed that a distinct 255-bp fragment corresponding to the sequence within MN/CA9 cDNA was detected in HeLa and SK-RC-52 cells, but SK-RC-29 cells did not have MN/CA9 transcripts. Western blot analysis demonstrated that HeLa and SK-RC-52 cells showed much stronger Ad5 E1a protein expressions compared with SK-RC-29. In vitro cytotoxicity assay revealed that the growth of MN/CA9-positive cells was significantly inhibited with 0.1-1MOI of Ad-MN/CA9-E1a, but the growth of MN/CA9-negative cells (SK-RC-29) could only be inhibited by as many as 100MOI.



Conclusions: These results suggest that a novel replication-competent adenoviral vector mediated by MN/CA9 promoter, Ad-MN/CA9-E1a, can selectively replicate in MN/CA9-expressing cancer cells with cytotoxic effects and may be utilized for the treatment of RCC.
Keywords
Renal cell carcinomaGene therapyAdenovirusVirus replication
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Urology
Full Text Link
Files in This Item:
456-462.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse