PMID- 10830724
OWN - NLM
STAT- MEDLINE
DCOM- 20000921
LR  - 20121115
IS  - 0929-1903 (Print)
IS  - 0929-1903 (Linking)
VI  - 7
IP  - 5
DP  - 2000 May
TI  - Preclinical study on gene therapy of cervical carcinoma using adeno-associated 
      virus vectors.
PG  - 766-77
AB  - Approximately 90% of cervical carcinomas are causally linked to infections with 
      high-risk human papillomaviruses (HPVs), whose oncogenicity has been assigned to 
      the continued expression of two early genes, E6 and E7. Reversal of the 
      transformed phenotype by inhibiting E6/E7 gene expression therefore provides a 
      suitable goal for future tumor therapy. Using recombinant adeno-associated virus 
      type 2 (AAV-2) vectors, two types of therapeutic genes were expressed in cervical 
      carcinoma cells with the aim of suppressing the E6/E7 oncogenes: (a) antisense 
      E6/E7 and ribozyme genes and (b) the monocyte chemoattractant protein-1 (MCP-1) 
      gene encoding MCP-1. Previous studies have shown that the MCP-1 protein is able 
      to indirectly repress E6/E7 gene expression and is consistently absent in 
      tumorigenic HPV-positive cervical carcinoma cell lines. Here, the effect of these 
      therapeutic genes on tumor formation is analyzed in nude mice after ex vivo gene 
      transfer into a HPV16- or HPV18-positive cervical carcinoma cell line (HeLa or 
      SiHa, respectively). Whereas AAV-2 vector-mediated transfer of antisense or even 
      ribozyme genes did not significantly influence tumor formation from implanted 
      SiHa cells, the transfer and expression of human MCP-1 strongly inhibited the 
      development of tumors derived from either HeLa or SiHa cells. Similar results 
      were also obtained after in vivo delivery of these genes into SiHa-derived 
      tumors. This suggests that transfer of therapeutic genes mediating a systemic 
      effect via recombinant AAV-2 vectors offers a promising approach for the 
      development of gene therapies directed against papillomavirus-induced human 
      cancers.
FAU - Kunke, D
AU  - Kunke D
AD  - Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte 
      Tumorvirologie, Heidelberg, Germany.
FAU - Grimm, D
AU  - Grimm D
FAU - Denger, S
AU  - Denger S
FAU - Kreuzer, J
AU  - Kreuzer J
FAU - Delius, H
AU  - Delius H
FAU - Komitowski, D
AU  - Komitowski D
FAU - Kleinschmidt, J A
AU  - Kleinschmidt JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Chemokine CCL2)
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (RNA, Catalytic)
RN  - 0 (Repressor Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Division/drug effects
MH  - Chemokine CCL2/genetics
MH  - Dependovirus/*genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors
MH  - HeLa Cells
MH  - Humans
MH  - Macrophages/cytology/drug effects
MH  - Mice
MH  - Mice, Nude
MH  - Models, Genetic
MH  - Oligonucleotides, Antisense/genetics
MH  - Oncogene Proteins, Viral/genetics
MH  - Papillomavirus E7 Proteins
MH  - Plasmids/genetics
MH  - RNA, Catalytic/genetics
MH  - *Repressor Proteins
MH  - Time Factors
MH  - Tumor Cells, Cultured
MH  - Uterine Cervical Neoplasms/*therapy
MH  - beta-Galactosidase/metabolism
EDAT- 2000/06/01 09:00
MHDA- 2000/09/23 11:01
CRDT- 2000/06/01 09:00
PHST- 2000/06/01 09:00 [pubmed]
PHST- 2000/09/23 11:01 [medline]
PHST- 2000/06/01 09:00 [entrez]
AID - 10.1038/sj.cgt.7700178 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2000 May;7(5):766-77. doi: 10.1038/sj.cgt.7700178.