Trends in Molecular Medicine
Id genes and proteins as promising targets in cancer therapy
Section snippets
Ids and tumorigenesis
Oncogenesis and metastasis are distinct, but related phenotypes. Oncogenecity is necessary, but not sufficient, for metastasis. Id genes have been suggested to act as cooperating oncogenes, as well as dominant oncogenes, based on the evidence that Id genes can immortalize primary rodent fibroblasts when co-transfected with the Bcl-2 gene, and that Id1 transfected alone can immortalize primary human keratinocytes 8, 12, 14, 16. Ectopic expression of Id1, Id2 and Id3 has been reported to extend
Id expression in primary tumor cells
The role of Id proteins in cancer progression has been a major focus of Id research. Numerous studies have analyzed the expression of Id genes in various cancer types, and compared these levels with Id expression levels in their respective normal tissue counterparts 12, 14, 15. Id1 expression has primarily been associated with more aggressive and invasive, as well as less differentiated (i.e. higher grade), tumor phenotypes; Id2 and Id3 have been shown to exhibit reciprocal expression patterns
Id proteins as targets for cancer therapy
Although the clinical relevance of Id expression in some cancer types has now been shown, the potential functional involvement of Id protein in cancer progression and metastasis has only recently been elucidated. Molecular pathways that are induced by the ectopic overexpression of Id genes have primarily focused on cell-cycle regulation and proliferation 8, 10, 12, 13, 59, 60. Studies of other cellular pathways that are affected by manipulating Id expression have pointed to several crucial
Concluding remarks
Future cancer therapy will focus on exploiting our growing knowledge of the role of cancer-causing genes and pathways in oncogenesis, as well in lethal metastatic spread. Based on this growing understanding of the molecular pathogenesis of human malignancies, more selective and more personalized therapies might be developed, with therapies targeting the molecular pathology of individual patients and their malignancies. It has been proposed that Id genes and proteins are excellent candidates for
Acknowledgements
The authors thank Andrew P. Smith for editing and Stephanie Kekulawela for literature searching and copying. The authors are supported by grants from NIH-NCI (RO1 CA82575 to R.J.D. and RO1 CA82548 to P-Y.D.) and from the California Breast Cancer Research Program (8WB-0164 to R.J.D. and 5IB-0111 and 7WB-0026 to P-Y.D.).
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