Rplp1 bypasses replicative senescence and contributes to transformation

• Published in: Experimental cell research 2009-05, Vol.315 (8), p.1372-1383
• Main Authors: Artero-Castro, A., Kondoh, H., Fernández-Marcos, P.J., Serrano, M., y Cajal, S. Ramón, LLeonart, M.E.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; AGAR; AGING; Animals; BIOPSY; BYPASSES; Cancer; Cell Line, Tumor; CELL PROLIFERATION; Cell Transformation, Neoplastic - metabolism; Cellular aging and senescence; Cellular biology; Cellular Senescence - physiology; Deoxyribonucleic acid; DNA; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; Embryonic stem cells; FIBROBLASTS; Gene Expression Regulation; GENES; Genetics; Humans; IN VITRO; LARGE INTESTINE; MESSENGER-RNA; MICE; MUTANTS; Mutation; NEOPLASMS; NIH 3T3 Cells; Phosphoproteins - metabolism; PROTEINS; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal proteins; Ribosomal Proteins - metabolism; RNA, Messenger - metabolism; Rodents; Signal Transduction; STEM CELLS; Tumor Suppressor Protein p53 - genetics; Up-Regulation
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2009.02.007

To determine whether genes expressed by embryonic stem cells have a proliferative effect in primary cells, primary mouse embryonic fibroblasts were infected with an ES cell cDNA library. This led to identification of the ribosomal protein, Rplp1, a member of the P group of ribosomal proteins, whose putative role for bypassing replicative senescence in MEFs was investigated. Our results show that Rplp1 produces a two-fold increase in the expression of an E2F1 promoter and upregulation of cyclin E in MEFs. Therefore, this study is the first to show that overexpression of a single ribosomal protein, Rplp1, is a cause and not a consequence of cell proliferation. In addition, co-expression of Rplp1 with mutant ras Val12 contributed to transformation in NIH3T3 cells, as was evidenced by colony production in soft-agar assays. Moreover, the Rplp1 protein was upregulated in MEFs and NIH3T3 cells upon expression of a p53 dominant negative mutant gene designated p53R175H. Hence, mutation of p53 may facilitate immortalization in vitro by upregulating Rplp1. Lastly, Rplp1 mRNA was found to be upregulated in 16 of 26 human colon cancer biopsy specimens, a finding that may be of relevance to cancer research.