RB -mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb +/− mice
Open Access
- 30 March 1999
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 96 (7), 3916-3921
- https://doi.org/10.1073/pnas.96.7.3916
Abstract
Alterations in pathways mediated by retinoblastoma susceptibility gene (RB) product are among the most common in human cancer. Mice with a single copy of the Rb gene are shown to develop a syndrome of multiple neuroendocrine neoplasia. The earliest Rb-deficient atypical cells were identified in the intermediate and anterior lobes of the pituitary, the thyroid and parathyroid glands, and the adrenal medulla within the first 3 months of postnatal development. These cells form gross tumors with various degrees of malignancy by postnatal day 350. By age of 380 days, 84% of Rb+/− mice exhibited lung metastases from C-cell thyroid carcinomas. Expression of a human RB transgene in the Rb+/− mice suppressed carcinogenesis in all tissues studied. Of particular clinical relevance, the frequency of lung metastases also was reduced to 12% in Rb+/− mice by repeated i.v. administration of lipid-entrapped, polycation-condensed RB complementary DNA. Thus, in spite of long latency periods during which secondary alterations can accumulate, the initial loss of Rb function remains essential for tumor progression in multiple types of neuroendocrine cells. Restoration of RB function in humans may prove an effective general approach to the treatment of RB-deficient disseminated tumors.Keywords
This publication has 58 references indexed in Scilit:
- Tumour-suppressor genes: evolving definitions in the genomic ageNature Genetics, 1997
- Delivery of a PCR amplified DNA fragment into cells: a model for using synthetic genes for gene therapyGene Therapy, 1997
- Cancer Cell CyclesScience, 1996
- Early loss of the retinoblastoma gene is associated with impaired growth inhibitory innervation during melanotroph carcinogenesis in Rb+/- mice.Genes & Development, 1996
- The amino-terminal region of the retinoblastoma gene product binds a novel nuclear matrix protein that co-localizes to centers for RNA processing.The Journal of cell biology, 1994
- Expression of a retinoblastoma transgene results in dwarf mice.Genes & Development, 1993
- Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesisNature, 1992
- A genetic model for colorectal tumorigenesisCell, 1990
- The Clonal Evolution of Tumor Cell PopulationsScience, 1976
- Suppression of Malignancy by Cell FusionNature, 1969