In vitro expression of the diphtheria toxin A-chain gene under the control of human chorionic gonadotropin gene promoters as a means of directing toxicity to ovarian cancer cell lines.
OBJECTIVE
Our goal was to determine whether toxicity of the diphtheria toxin A-chain gene regulated by the human chorionic gonadotropin promoter can be directed to malignant ovarian cell lines.


METHODS
Plasmids containing diphtheria toxin A-chain gene linked to the regulatory elements of the metalloergothioneine and human chorionic gonadotropin promoters were transfected into the cell lines. Expression of diphtheria toxin A-chain gene was determined by the inhibition of a cotransfected luciferase reporter gene.


RESULTS
Cytotoxicity of the diphtheria toxin A-chain gene is shown in a dose-responsive manner. Transfection of a plasmid expressing the diphtheria toxin A-chain gene controlled by a constitutive promoter readily inhibits protein synthesis. Specific inhibition of luciferase protein synthesis occurs in ovarian cancer cells transfected with the diphtheria toxin A-chain gene under the control of the human chorionic gonadotropin promoters when compared with normal ovarian epithelial cells or fibroblasts.


CONCLUSIONS
These data demonstrate the preferential expression of the diphtheria toxin A-chain gene, regulated by the human chorionic gonadotropin promoter, to ovarian cancer cell lines. This provides an avenue for targeting such cells for suicide, toxin, or cytokine genes.
Lidor
Y J
YJ
Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver 80262, USA.
Lee
W E
WE
Nilson
J H
JH
Maxwell
I H
IH
Su
L J
LJ
Brand
E
E
Glode
L M
LM
D002277:Carcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D006063:Chorionic Gonadotropin / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis / Q000378:metabolism; D004167:Diphtheria Toxin / Q000235:genetics* / Q000502:physiology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D004167:Diphtheria Toxin; D010446:Peptide Fragments; C063554:urinary gonadotropin fragment; D008156:Luciferases