1. Tumors with nonfunctional retinoblastoma protein are killed by reduced γ-tubulin levels.
- Author
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Ehlén Å, Rosselló CA, von Stedingk K, Höög G, Nilsson E, Pettersson HM, Jirström K, and Alvarado-Kristensson M
- Subjects
- Animals, Caspase 3 genetics, Caspase 3 metabolism, Cell Line, Tumor, E2F1 Transcription Factor genetics, E2F1 Transcription Factor metabolism, Humans, Mice, NIH 3T3 Cells, Neoplasms genetics, Neoplasms therapy, Retinoblastoma Protein genetics, Tubulin genetics, Apoptosis, Neoplasms metabolism, Retinoblastoma Protein metabolism, Signal Transduction, Tubulin metabolism
- Abstract
In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and γ-tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and γ-tubulin protein levels results in an E2F1-dependent up-regulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of γ-tubulin and RB1 and that in tumor cell lines with a nonfunctioning RB1, reduction of γ-tubulin protein levels leads to induction of apoptosis. Thus, the RB1/γ-tubulin signal network can be considered as a new target for cancer treatment.
- Published
- 2012
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