Modulation of Cyclin Expression by c-Myc in Malignant and Nonmalignant Mammary Epithelial Cells.
Abstract
The experiments described here identified components of the pathways through which Myc acts to both increase proliferation and induce apoptosis in mammary epithelial cells (MECs). The accelerated growth of MECs which overexpress c-myc was due to a more rapid passage through the G1 phase of the cell cycle. AlN4-myc cells displayed constitutive hyperphosphorylation of the retinoblastoma protein, most likely as a result of elevated cdk2 activity. The high propensity of Myc83 cells to undergo apoptosis was associated with constitutive expression of Bax and p53. In contrast, Bcl-XL expression varied significantly with growth factor addition or removal. Bcl-XL protein levels were dramatically elevated in cells which were grown in the presence of EGF or TGFalpha compared to apoptotic cells which had been deprived of EGF or treated with TGFbeta. Mammary tumors arising in Myc/TGFalpha double transgenic mice also consistently showed a higher relative ratio of Bcl-XL/Bax than tumors from Myc single transgenic mice. Our results suggest an important role of Bcl-XL in the ability of EGF to act as a survival factor for MECs which overexpress c-Myc
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1996
- Accession Number
- ADA320400
Entities
People
- Robert B. Dickson
- Sharyl J. Nass
Organizations
- Georgetown University