Accession Number : ADA366723
Title : Programmed Cell Death in Breast Cancer
Descriptive Note : Final rept. 1 Oct 94-30 Sep 98
Corporate Author : CASE WESTERN RESERVE UNIV CLEVELAND OH
Personal Author(s) : Distelhorst, Clark W.
Report Date : OCT 1998
Pagination or Media Count : 41
Abstract : Programmed cell death, or apoptosis, is a genetically regulated process through which a cell is active in bringing about its own death for the sake of the entire organism. Apoptosis is the mechanism by which the mammary gland normally undergoes involution. Also, apoptosis is the mechanism by which many cancer chemotherapeutic agents induce the death of breast cancer cells. This work has focused on the role of intracellular calcium as a mediator of the apoptotic process in the MCF-7 and MDA-MB-468 breast cancer cell lines. The findings indicate that release of calcium from intracellular stores by the calcium-ATPase inhibitor, thapsigargin, induces apoptosis in these cell lines. However, the cells mount an endogenous stress response that delays and inhibits the cell death response, so that the breast cancer cell lines are much less susceptible to thapsigargin-induced apoptosis than lymphoid cell lines, an observation that parallels the differential susceptibility of breast cancer and lymphomas to chemotherapy-induced cell death in vitro. One component of this work still in progress is to measure how the stress responses, and well know apoptosis inhibitors like Bcl-2, regulate intracellular calcium fluxes that mediate apoptosis. Ultimately, this work will provide new insight into the role of calcium in the apoptotic process in breast cancer cells and how the response of cells to apoptotic signals is regulated by endogenous stress responses.
Descriptors : *DEATH , *CELLS(BIOLOGY) , *BREAST CANCER , CALCIUM , ACTIVATION , HORMONES , STRESS(PHYSIOLOGY) , MAMMARY GLANDS , LYMPHOMAS.
Subject Categories : ANATOMY AND PHYSIOLOGY
MEDICINE AND MEDICAL RESEARCH
Distribution Statement : APPROVED FOR PUBLIC RELEASE