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The cell lines were characterized cytogenetically during their transformation from normal to spontaneously immortalization and were found to recapitulate many of the changes observed in human cancer cells such as the deregulation of oncogenes (Myc, Mdm2) and tumor suppressor genes (Cdnk4a/Ink4a/p16, Rb).
Carcinomas that arise from the epithelial cells lining organs lead to the most common cancers in humans. However, research on cellular transformation has largely relied on fibroblast cells which are not of epithelial origin and therefore, may not reflect the changes that lead to epithelial oncogenesis. The availability of these mouse epithelial cancer cell lines should allow for a more accurate analysis of this process.
The cell lines have unique properties that make them suitable for study of the following:
• Unlimited replicative potential.
• Exhibit tumorigenic potential and EMT (Epithelial Mesencymal Transition).
• Exhibit high degree of chromosome instability (chromosome rearrangements, amplifications) in regions orthologous to those altered in human cancers.
• Use in mapping mouse genes homologous to human cancer genes and for the study of the effects of deregulation of cancer associated genes, through silencing or overexpression.
• For use in gene expression studies of tumor progression, comparing profiles to human cancers involving the same tissue types.
• Use as experimental controls in the analysis of oncogene signaling pathways.
• Use in the studying telomerase pathway regulation (200-fold expression difference between cell lines).
• Use of mouse as model of epithelial carcinomas and specifically cancers of the bladder, cervix, colon, lung, mammarys and kidney cancers.
• These mouse models serve as vehicles to test the efficacy of new therapies, targeting specific targets associated with the transformation of six different mouse epithelial tissues.
• Use for discovering drugs that alter the tumorigenic potential, invasiveness, and the Epithelial-Mesenchymal Transition state.
• Cytogenetically defined epithelial cell lines from mouse that model human carcinomas.
• Spontaneously transformed primary cell cultures were generated from isogenic mouse strain that has a low propensity for epithelial tumors in vivo therefore, not involving other mouse strains potentially influencing the genetic background.
• These cell lines were generated without viral, chemical or genetic manipulation and thus can serve as mouse models for studying the natural process of oncogenesis and as mouse models of human cancers.
• Genomically defined colon, bladder, and kidney cell lines showing oncogene deregulation (i.e. Mdm2 and Myc overexpression).
• Ready for use.
• Pre-clinical.
The tumor samples made available herein contain deletions in the cyclic nucleotide phosphodiesterase (PDE) PDE7A or PDE8B genes that impair PDE function and are characterized by high sensitivity to changes in cAMP levels. Commercially, phosphodiesterase inhibitors are widely used in the treatment of various disorders, including asthma, pulmonary hypertension, and erectile dysfunction, suggesting a potential utility for these tissues in a wide range of investigations.
Akt, a serine/threonine kinase that can block apoptosis, has been implicated in the regulation of microtubule dynamics and organization. Akt phosphorylation and its transducing downstream events play a central role in cell survival and cell cycle progression at the G
Researchers at the National Cancer Institute, NIH, have identified pAkt as having predictive significance for paclitaxel chemotherapy outcome in patients with early stage breast cancer. The researchers have developed an immunohistochemistry method for determining pAkt status with appropriate controls for assay performance and cutoff for pAkt positivity. They also discovered methods of correlating pAkt expression with clinical outcome (disease-free survival and overall survival). pAkt is a novel predictive marker of taxane chemotherapy, and can be applied to indicate which patients should receive taxane-based chemotherapy.
1. Yang, SX, Costantino JP, Mamounas EP, Nguyen D, Jeong J–H, Wolmark N, Kim C, Kidwell K, Paik S, Swain SM. Correlation of levels of Akt phosphorylation at Ser473 with benefit from paclitaxel chemotherapy in NSABP B–28 patients with node-positive breast cancer. J Clin Oncol. 2009 (May 20 Supplement);27(15S):537.
2. Yang SX, Costantino JP, Mamounas EP, Nguyen D, Jeong J–H, Wolmark N, Kim C, Kidwell K, Paik S, Swain SM. Akt phosphorylation at Ser473 predicts benefit to paclitaxel chemotherapy in node-positive breast cancer. J Clin Oncol. 2010, In Press.