Tumor-suppressive effect of the retinoic acid receptor beta in human epidermoid lung cancer cells
| Autor: | Benoit Houle, Walter Edward Bradley, Cécile Rochette-Egly |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Lung Neoplasms Tumor suppressor gene Receptors Retinoic Acid Retinoic acid Mice Nude Tretinoin Retinoic acid receptor beta Simian virus 40 Biology Transfection medicine.disease_cause Mice chemistry.chemical_compound Internal medicine Tumor Cells Cultured medicine Animals Humans Genes Tumor Suppressor RNA Messenger Beta (finance) Lung cancer neoplasms Multidisciplinary medicine.disease Recombinant Proteins Neoplasm Proteins Endocrinology chemistry embryonic structures Chromosomal region Carcinoma Squamous Cell Cancer research Carrier Proteins Carcinogenesis Cell Division Research Article medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 90:985-989 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.90.3.985 |
| Popis: | Retinoic acid receptor beta (RAR beta), which codes for a nuclear receptor for retinoic acid, is localized in a chromosomal region frequently deleted in lung cancer cells. The gene is expressed in normal lung tissue and in the majority of the cell lines derived from lung tumors but not in most of the lines derived from lung tumors with epidermoid characteristics. To study the possible role of RAR beta in growth control of epidermoid lung tumor-derived cells, transfectants expresing RAR beta were generated from nonexpressing epidermoid tumor-derived cell lines. Four clones were derived from line CALU-1, three of which showed a 20-60% increase in doubling time in the presence of retinoic acid. Parental and control-transfected cells were unaffected or slightly stimulated. All four clones expressing RAR beta were less tumorigenic in nude mice than were the untransfected or control-transfected cells, with about a 50% incidence of take vs. 95%. When tumors did develop from RAR beta-positive cells, they showed a reduced rate of growth, an increased latency, and, in six of seven tumors tested, a much reduced level of RAR beta expression. Transfectants derived from a second tumor line, H157, also showed a markedly reduced incidence of take in nude mice. Together with the known effects of retinoic acid on differentiation and carcinogenesis, our results support the hypothesis that RAR beta functions as a tumor suppressor gene in epidermoid lung tumorigenesis. |
| Databáze: | OpenAIRE |
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