Accession Number : ADA300314

Title :   Function of Cell Cycle Control Proteins in Breast Cancer.

Descriptive Note : Annual rept. 1 Aug 94-31 Jul 95,

Corporate Author : HARVARD MEDICAL SCHOOL BOSTON MA

Personal Author(s) : Hinds, Philip W.

PDF Url : ADA300314

Report Date : 31 AUG 1995

Pagination or Media Count : 13

Abstract : Loss of the retinoblastoma tumor suppressor protein (pRb) can contribute to breast tumor formation. However, many breast tumors retain expression of normal pRb, indicating that other genetic events may interfere with the function of this growth regulatory protein. Overexpression of cyclin D 1 is such an event, since high levels of this protein may lead to constitutive inactivation of pRb through phosphorylation. We have demonstrated that cyclin Dl in oncogenic in cultured cells, and are using this assay to define regions and functions of cyclin Dl needed for transformation. Interestingly, a previously defined pRb-interaction domain in cyclin D 1 is dispensable for transformation in cyclin Dl, but apparently not in the closely related cyclin D2. Instead, loss of a cyclin Dl domain just C-terminal the pRb-interaction domain may inactivate the protein. Using our knowledge of cyclin Dl function from these mutants and others we hope to eventually create animal models of Di-dependent tumorigenesis useful for identifying suppressors of these tumors.

Descriptors :   *MAMMARY GLANDS, *BREAST CANCER, CELLS, PROTEINS, NEOPLASMS, CYCLES, MUTATIONS, LIFE CYCLES, GENETICS, CANCER, SUPPRESSORS, PHOSPHORYLATION.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE