Induction of the expression of differentiation-related antigens on human colon carcinoma cells by stimulating protein kinase C
P. L. Baron, M. J. Koretz, R. A. Carchman, J. M. Collins, A. S. Tokarz and G. A. Parker
Department of Surgery Medical College of Virginia/Virginia Commonwealth University, Richmond.
This study was undertaken to determine whether the phorbol diester, phorbol
12-myristate 13-acetate (PMA), causes differentiation of the human colon
carcinoma cell line, SW 48. Under routine growth conditions, the cells are
round, have a high nuclear-to-cytoplasmic ratio, and lack cytoplasmic
vacuoles. After treatment for 1 hour with 100 nmol/L of PMA at 37 degrees
C, the cells assumed a spread-out, flasklike shape, displayed a low
nuclear-to-cytoplasmic ratio, and exhibited cytoplasmic vacuoles. An inert
but lipophilic phorbol diester, 4 phorbol 12,13-didecanoate, failed to
induce these morphological changes. Cell kinetic studies showed that
whereas SW 48 cells have a doubling time of 35 hours, those incubated with
100 nmol/L of PMA have a doubling time of 90 hours. Although the flow
cytometry histograms were similar until 8 hours into the cell cycle, the
PMA-treated cells ultimately spent proportionately less time in S and more
in G2/M. Finally, under routine growth conditions, SW 48 cells express
neither carcinoembryonic antigen nor G7 antigen. These antigens, which are
present on the surface of well-differentiated cells, were expressed after
treatment of SW 48 with PMA. The data suggest that PMA causes profound
changes in structure, cell growth kinetics, and antigen expression,
consistent with induction of differentiation of the cell line SW 48.
