Oncogene database

2475

MTOR

mechanistic target of rapamycin (serine/threonine kinase);MTOR;mechanistic target of rapamycin (serine/threonine kinase)

FK506 binding protein 12-rapamycin associated protein 2|FK506-binding protein 12-rapamycin complex-associated protein 1|FKBP-rapamycin associated protein|FKBP12-rapamycin complex-associated protein 1|mammalian target of rapamycin|rapamycin and FKBP12 targ

1p36.2

protein-coding

DNA damage has been thought to be directly associated with the neoplastic progression by enabling mutations in tumor suppressor genes and activating/and amplifying oncogenes ultimately resulting in genomic instability. DNA damage causes activation of the DNA damage response (DDR) that is an important cellular mechanism for maintaining genomic integrity in the face of genotoxic stress. While the cellular response to genotoxic stress has been extensively studied in cancer models, less is known about the cellular response to oncogenic stress in the premalignant context. In the present study, by using breast tissues samples from women at different risk levels for invasive breast cancer (normal, proliferative breast disease and ductal carcinoma in situ) we found that DNA damage is inversely correlated with risk of invasive breast cancer. Similarly, in MCF10A based in vitro model system where we recapitulated high DNA damage conditions as seen in patient samples by stably cloning in cyclin E, we found that high levels of oncogene induced DNA damage, by triggering inhibition of a major proliferative pathway (AKT), inhibits cell growth and causes cells to die through autophagy. These data suggest that AKT-mTOR pathway is a novel component of oncogene induced DNA damage response in immortalized normal-like breast cells and its suppression may contribute to growth arrest and arrest of the breast tumorigenesis.