p27 and Rb are on overlapping pathways suppressing tumorigenesis in mice Journal Article
| Authors: | Park, M. S.; Rosai, J.; Nguyen, H. T.; Capodieci, P.; Cordon-Cardo, C.; Koff, A. |
| Article Title: | p27 and Rb are on overlapping pathways suppressing tumorigenesis in mice |
| Abstract: | The commitment of cells to replicate and divide correlates with the activation of cyclin-dependent kinases and the inactivation of Rb, the product of the retinoblastoma tumor suppressor gene, Rb is a target of the cyclin-dependent kinuses and, when phosphorylated, is inactivated. Biochemical studies exploring the nature of the relationship between cyclin- dependent kinase inhibitors and Rb have supported the hypothesis that these proteins are on a linear pathway regulating commitment. We have been able to study this relationship by genetic means by examining the phenotype of Rb+/- p27-/- mice. Tumors arise from the intermediate lobe cells of the pituitary gland in p27 -/- mice, as well as in Rb+/- mice after loss of the remaining wild-type allele of Rb. Using these mouse models, we examined the genetic interaction between Rb and p27. We found that the development of pituitary tumors in Rb+/- mice correlated with a reduction in p27 mRNA and protein expression. To determine whether the loss of p27 was an indirect consequence of tumor formation or a contributing factor to the development of this tumor, we analyzed the phenotype of Rb+/-p27-/- mice. We found that these mice developed pituitary adenocarcinoma with loss of the remaining wild-type allele of Rb and a high-grade thyroid C cell carcinoma that was more aggressive than the disease in either Rb+/- or p27 -/- mice. Importantly, we detected both pituitary and thyroid tumors earlier in the Rb+/-p27-/- mice. We therefore propose that Rb and p27 cooperate to suppress tumor development by integrating different regulatory signals. |
| Keywords: | immunohistochemistry; signal transduction; survival; protein expression; nonhuman; animal cell; mouse; phenotype; animals; cell cycle proteins; mice; mice, knockout; animal tissue; cell division; animal model; protein binding; genotype; transcription, genetic; enzyme activation; heterozygote; carcinogenesis; animalia; tumor suppressor gene; rna, messenger; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; aging; rodentia; senescence; cyclin-dependent kinases; cyclin dependent kinase inhibitor; retinoblastoma protein; genes, tumor suppressor; rna analysis; microtubule-associated proteins; pituitary gland; pituitary neoplasms; genes, retinoblastoma; thyroid cell; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 96 |
| Issue: | 11 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1999-05-01 |
| Start Page: | 6382 |
| End Page: | 6387 |
| Language: | English |
| DOI: | 10.1073/pnas.96.11.6382 |
| PUBMED: | 10339596 |
| PROVIDER: | scopus |
| PMCID: | PMC26890 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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181Rosai -
612Cordon-Cardo -
19
Capodieci
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