The Importance of Autophagy in Breast Cancer Development and Treatment
Abstract
Autophagy, a conserved, programmed response to metabolic and environmental stress found in yeast, plants, worms, flies, mice, and man 1, has been known to play a critical role in the regulation of survival and death of various types of cells 2. Recent studies have implicated autophagy in a number of physiologic and pathophysiologic processes such as aging, cancers, and neurodegenerative diseases 3. The process of autophagy involves formation of doublemembrane vesicles (autophagosomes) that engulf organelles and cytoplasm, then fuses with the lysosome to form the autolysosme, where the contents are degraded and recycled for protein and ATP synthesis 4, 5. The formation of the autophagosome is mediated by a series of autophagy - promoting gene products that function at different stages of autophagy 6. Beclin 1, the mammalian homologue of the yeast Atg6, is a key autophagy - promoting gene whose product is part of a lipid kinase (class III Phosphoinositide 3-kinase) complex that participates in the early stage of autophagosome formation 7, 8. Beclin 1 is a ~60-kDa coiled - coli protein also able to interact with bcl-2, an anti-apoptotic protein. Although ubiquitously expressed, it has been known that the expression of beclin 1 is altered in certain diseases. For example, in early Alzheimer disease beclin 1 expression is decreased 9; in contrast, neurodegeneration causes up-regulation of beclin 1 10. In several types of human cancers, the expressions of beclin 1, both protein and mRNA, were also found to be aberrant 11-13. Yet, the causes underlying the altered expression of this key autophagy - promoting gene remains largely unknown. In the present study we sought to explore the role of microRNAs (miRNAs) in the regulation of expression of beclin 1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2009
- Accession Number
- ADA514019
Entities
People
- Jin-ming Yang
Organizations
- Penn State College of Medicine