Accession Number : ADA328990

Title :   The Role of the Novel Nuclear Tyrosine Kinase, RAK, in Breast Cancer Biology

Descriptive Note : Annual rept. 1 Jul 96-30 Jun 97

Corporate Author : NORTH CAROLINA UNIV AT CHAPEL HILL

Personal Author(s) : Liu, Edison ; Craven, Rolf

PDF Url : ADA328990

Report Date : JUL 1997

Pagination or Media Count : 9

Abstract : The Rak tyrosine kinase is a 54 kDa protein with SH2 and SH3 domains at its amino terminus. Although Rak resembles the Src-related kinases structurally, Rak differs in that it is expressed primarily in epithelial cells and localizes to the nucleus. We have found that Rak inhibits the growth of NIH 3T3 cells as determined by a colony formation assay. Furthermore, induction of Rak expression from a dexamethasone-inducible promoter leads to enlarged, flattened cells. There are two potential effectors of Rak's growth inhibitory activity, Rak binds to the retinoblastoma tumor suppressor protein pRb and the cell cycle regulatory kinase CDC2. However, we have found that Rak inhibited growth equally in the Rb+ osteosarcoma cell line U2- Os and the Rb-minus osteosarcoma cell line Saos-2, suggesting that binding to Rb is not required for Rak's biological activity. The parallel experiment for CDC2 was not possible because CDC2 is an essential gene. Finally, we have found that Rak localizes to chromosome 6q21. This site is frequently altered in a variety of human tumors, including breast tumors. Thus, Rak is a kinase with growth inhibitory activity that localizes to a putative tumor suppressor locus.

Descriptors :   *TYROSINE, *PHOSPHORUS TRANSFERASES, *BREAST CANCER, EPITHELIUM, HORMONES, HUMANS, PROTEINS, NEOPLASMS, DEOXYRIBONUCLEIC ACIDS, CLONES, INHIBITION, CELLS(BIOLOGY), RIBONUCLEIC ACIDS, AMINO ACIDS, MAMMARY GLANDS, SUPPRESSORS, GROWTH(PHYSIOLOGY), IMMUNOCHEMISTRY.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE