Adenovirus-mediated retinoblastoma gene therapy suppresses spontaneous pituitary melanotroph tumors in Rb+/- mice.
The retinoblastoma gene (RB) is the prototypic tumor suppressor. Studies to date have demonstrated cancer suppression with tumor cells reconstituted with RB ex vivo and implanted into immunodeficient mice, as well as with germline transmission of a human RB transgene into tumor-prone Rb +/- mice. To mimic the therapy of cancer more closely, spontaneous pituitary melanotroph tumors arising in immunocompetent Rb +/- mice were treated with a recombinant adenovirus carrying RB cDNA. Intratumoral RB gene transfer decreased tumor cell proliferation, reestablished innervation by growth-regulatory dopaminergic neurons, inhibited the growth of tumors, and prolonged the life spans of treated animals.
Riley
D J
DJ
Center for Molecular Medicine, University of Texas Health Science Center at San Antonio 78245, USA.
Nikitin
A Y
AY
Lee
W H
WH
D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D016161:Genes, Retinoblastoma / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D010902:Pituitary Gland / Q000737:chemistry / Q000294:innervation; D010911:Pituitary Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein