INFLUENCE OF CELL-PROLIFERATION AND CELL-CYCLE PHASE ON EXPRESSION OF ESTROGEN-RECEPTOR IN MCF-7 BREAST-CANCER CELLS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (2) , 619-625
Abstract
The effects of cell cycle phase and proliferation rate on the expression of specific estrogen binding activity were explored in hormone-dependent human breast cancer cells. A technique was developed to alter the proliferative rate of MCF-7 cells by plating at different densities. The doubling time ranged from 20 to 48 h, showing a negative relation to the number of plated cells. Slowly proliferating cells had accumulated more than twice as much estrogen receptor (ER) activity as did fast-proliferating cells. Exposure of exponentially growing cells to isoleucine-deficient medium resulted in decreased thymidine incorporation and disappearance of detectable cellular ER activity. Overall protein synthesis was reduced by only 30% in cells growing in isoleucine-free medium. At 24 h after release from isoleucine deprivation, ER levels are fully restored, although thymidine incorporation does not resume for an additional 6-8 h, and increases in cell number are not seen for 24 h. Exposure of exponentially growing cells to 2 mM thymidine for 24 h produced partially synchronized MCF-7 cells (.apprx. 70%). Six hours after release from excess thymidine, cells reached S phase; after 9 hr, G2; and after 18 h, G1. ER levels immediately and, 6 h after release, remained unchanged, showed a slight increase at 9 h, and showed an increase of about 50-60% at 18 h. These data suggest that: ER binding activity and DNA synthesis can be dissociated; ongoing protein synthesis is necessary for maintenance of cellular ER activity; and ER is apparently synthesized throughout the cell cycle, with some evidence that this is predominantly in G1 and G2. [The therapeutic implications are discussed.].