Accession Number : ADA337560

Title :   The Role of HAP Kinases in Breast Cancer.

Descriptive Note : Annual rept. 29 Aug 96-28 Aug 97

Corporate Author : MASSACHUSETTS GENERAL HOSPITAL BOSTON

Personal Author(s) : Kyriakis, John M.

PDF Url : ADA337560

Report Date : SEP 1997

Pagination or Media Count : 19

Abstract : Our research has focused this year on the signal transduction pathways by which tumor necrosis factor (mW) activates the stress-activated protein kinases (SAPKs, also called Jun N-terminal Itinases, JNKs) and the p38s. TNF can promote the apoptotic death of breast cancer cells and exploitation of the proapoptotic signaling pathways mediated by TNF could prove efficacious in the treatment of breast cancer. Alternatively, inasmuch as the SAPK and p38 pathways are activated by many agents commonly used to treat cancer (ionizing radiation, genotoxins such as cisplatin and etoposide, for example) inhibition of these stress-regulated signaling pathways could reduce the disfiguring side effects of cancer treatments. Our results indicate that the mT receptor associated factor 2 (TRAF2) protein mediates SAPK and p38 activation by physically associating with two proximal protein kinases: germinal center kinase (GCK) and receptor interacting protein (RIP). GCK and RIP, in turn, associate with mitogen-activated protein Icinase-kinase-kinases (MAP3Ks) upstream of the SAPKs and p38s. We have succeeded in generating an MCF7 breast carcinoma cell line which stably expresses GCK under the control of a tetracyclin- inducible promoter. These cells will be used in studies of the biology of OCK signaling.

Descriptors :   *NEOPLASMS, *TOXINS AND ANTITOXINS, *NECROSIS, *PHOSPHORUS TRANSFERASES, *BREAST CANCER, BIOLOGY, INTERACTIONS, ENZYMES, PROTEINS, SIGNALS, TOXIC AGENTS, TRANSDUCERS, INHIBITION, DEATH, CELLS(BIOLOGY), IONIZING RADIATION, SENSE ORGANS, PHOSPHORYLATION.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE