Accession Number : ADA320400

Title :   Modulation of Cyclin Expression by c-Myc in Malignant and Nonmalignant Mammary Epithelial Cells.

Descriptive Note : Annual rept. 1 Sep 95-31 Aug 96,

Corporate Author : GEORGETOWN UNIV WASHINGTON DC

Personal Author(s) : Dickson, Robert B. ; Nass, Sharyl J.

PDF Url : ADA320400

Report Date : SEP 1996

Pagination or Media Count : 50

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

Descriptors :   *EPITHELIUM, *MODULATION, *MAMMARY GLANDS, *BREAST CANCER, RATIOS, SURVIVABILITY, PROTEINS, NEOPLASMS, CYCLES, GENES, RETINA, MICE, CELLS(BIOLOGY), GROWTH(PHYSIOLOGY).

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE