Nuclear Patch Clamping for Determining Ion Channel Activities of Bcl Apoptosis Proteins in Endoplasmic Reticulum and Nuclear Envelope Intracellular Membranes
Abstract
Apoptosis, the morphological and biochemical manifestation of programmed cell death, plays a critical role in maintaining homeostasis of tissue and organ cell number, and is involved in differentiation, growth and development (1-4). Mammary gland physiology is strongly influenced by apoptosis in both normal and pathologic states. Involution of the lactating gland is due to apoptosis of differentiated epithelial cells, and an emerging hypothesis is that dysfunction of the apoptotic pathways in mammary gland is significantly involved in the causes and progression of breast cancer (5-9). Thus, definition of the biochemical pathways involved in mammary gland apoptosis is an important goal in breast cancer research. An important regulator of apoptosis is the bcl-2 oncogene (2,5). Bcl-2 expression prevents apoptosis in several cell types and is associated with a poor prognosis in response to various cancer therapies in patients. Bcl-2 is normally expressed at high levels in some tissues, including mammary gland. More recently, other bcl-2- related genes have been identified, defining a gene family. Like bcl-2, some are anti-apoptotic, whereas others promote apoptosis. It is likely that the pro:anti -apoptotic expression level ratio regulates sensitivity to apoptosis. Breast cancer is associated with an altered ratio, which correlates with failure to respond to therapy and poor survival (7-9). Thus, many breast cancers may be diseases of apoptosis. The molecular mechanisms which link bcl proteins to apoptosis are undefined, although bcl proteins act at a critical juncture which integrates different death signals and activates a single death pathway. Intracellular Ca2+ and intracellular Ca2+ stores may be involved in regulating apoptosis, and expression of bcl-2 has been linked to alterations in Ca2+ signaling and in the handling of Ca2+ by intracellular stores, including the endoplasmic reticulum (ER) and mitochondria (4,10-13).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA404543
Entities
People
- J. K. Foskett
Organizations
- University of Pennsylvania