Abstract
The retinoblastoma gene family consisting of RB/p105, p107, and RB2/p130 cooperate to regulate cell-cycle progression through the G1 phase of the cell cycle. Previous data demonstrated an independent role for the reduction or loss of pRb2/p130 expression in the formation and/or progression of lung carcinoma. Rb2/p130 is mutated in a human cell line of lung small cell carcinoma as well as in primary lung tumors. To identify potential pRb2/p130 target genes in an unbiased manner, we have utilized an adenovirus-mediated expression system of pRb2/p130 in a non-small lung cancer cell line to identify specific genes that are regulated by pRb2/p130. Using oligonucleotide arrays, a number of Rb2/p130 downregulated genes were identified and their regulation was confirmed by semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) and Western blot analysis. As a result, 40 genes showed greater than 2.0-fold modification in their expression level after the RB2/p130 viral transduction. In conclusion, coupling adenoviral overexpression with microarray and semiquantitative RT–PCR analyses proved to be a versatile strategy for identifying pRb2/p130 target genes and for better understanding the expression profiles of these genes. Our results may also contribute to identifying novel therapeutic biomarkers in lung carcinoma.
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Acknowledgements
This work was supported by NIH grants and the Sbarro Health Organization to AG. G.R. acknowledges the Ph.D. program: “Diagnostic, quantitative, and molecular pathology” of the University of Siena, Italy.
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Russo, G., Claudio, P., Fu, Y. et al. pRB2/p130 target genes in non-small lung cancer cells identified by microarray analysis. Oncogene 22, 6959–6969 (2003). https://doi.org/10.1038/sj.onc.1206866
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DOI: https://doi.org/10.1038/sj.onc.1206866
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