Role in MYC in Anchorage-Dependent Growth.
Abstract
When deprived of adhesion to solid substrate, non-hematopoietic, normal cells are unable to proliferate; instead, they arrest in the 61 phase of the cell cycle. Unlike normal cells, transformed cells are able to bypass this integrin-mediated control of proliferation and to grow in an anchorage-independent manner. Understanding the mechanism by which the extracellular matrix controls progression through the 61 phase of the cell cycle would give us insight into cellular alterations that accompany carcinogenesis. We have shown, here using a mammary epithelial model, that the expression of the early growth control gene, c-Myc, is directly regulated by cell adhesion through a 31 integrin-dependent pathway. When deprived of adhesion, mammary epithelial cells are unable to progress into S phase upon EGF stimulation, and they arrest in early 61. This anchorage-dependent 61 block correlates with the downregulation of c-Myc mRNA and protein. Overexpression of c-Myc in these cells overcomes the 61 block, allowing for and anchorage independent downregulation of p27, activation of cyclin E-CDK2, and progression into S phase. Our study shows that c-myc is a crucial player in mediating anchorage-dependent control of cell cycle progression in human mammary epithelial cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA377816
Entities
People
- Christelle Benaud
Organizations
- Georgetown University