Suppression of GRP78 halts tumor growth and activation of AKT in mouse model, according to PNAS study.
Researchers at the University of Southern California working with mice have found that inactivating a specific biomarker for aggressive prostate cancer blocks the development of the cancer when PTEN, a powerful tumor suppressor gene for a number of human cancers, is missing.
The glucose-regulated protein GRP78 has been identified as a crucial entity in the development of prostate cancer by promoting cancer cell proliferation, mediating oncogenic signaling, and protecting cancer cells against cell death resulting from the stress of tumor development.
“To our knowledge, this is the first demonstration that inactivation of a specific molecular chaperone from the mouse prostate epithelial cells can potently block prostate cancer development and suppress the activation of AKT, which is a protein kinase that promotes cell proliferation and survival and is a major factor in many types of cancer,” says Amy Lee, Ph.D., the study's principal investigator.
Researchers spent more than three years monitoring prostate cancer development in animal models that had been genetically engineered to have both the GRP78 and PTEN tumor suppressor genes inactivated.
Future research will test the role of GRP78 in other types of cancer and isolate drugs that inhibit GRP78.
The article appears online currently in Proceedings of the National Academy of Sciences.