Restoration of adenylate cyclase responsiveness in murine myeloid leukemia
permits inhibition of proliferation by hormone. Butyrate augments catalytic
activity of adenylate cyclase
L Inhorn, JW Fleming, D Klingberg, TG Gabig and HS Boswell
Department of Medicine, Indiana University School of Medicine, Indianapolis
46223.
Mechanisms of leukemic cell clonal dominance may include aberrations of
transmembrane signaling. In particular, neoplastic transformation has been
associated with reduced capacity for hormone-stimulated adenylate cyclase
activity. In the present study, prostaglandin E, a hormonal activator of
adenylate cyclase that has antiproliferative activity in myeloid cells, and
cholera toxin, an adenylate cyclase agonist that functions at a
postreceptor site by activating the adenylate cyclase stimulatory
GTP-binding protein (Gs), were studied for antiproliferative activity in
two murine myeloid cell lines. FDC-P1, an interleukin 3 (IL 3)-dependent
myeloid cell line and a tumorigenic IL 3- independent subline, FI, were
resistant to these antiproliferative agents. The in vitro ability of the
"differentiation" agent, sodium butyrate, to reverse their resistance to
adenylate cyclase agonists was studied. The antiproliferative action of
butyrate involved augmentation of transmembrane adenylate cyclase activity.
Increased adenylate cyclase catalyst activity was the primary alteration of
this transmembrane signaling group leading to the functional inhibitory
effects on leukemia cells, although alterations in regulatory G- proteins
appear to play a secondary role.
Volume 71,
Issue 4,
pp. 1003-1011,
04/01/1988
Copyright © 1988 by The American Society of Hematology
