Ra. Majack, EXTINCTION OF AUTONOMOUS GROWTH-POTENTIAL IN EMBRYONIC-ADULT VASCULARSMOOTH-MUSCLE CELL HETEROKARYONS, The Journal of clinical investigation, 95(2), 1995, pp. 464-468
Vascular smooth muscle cells (SMC) isolated from embryonic and early f
etal (e13-e18) rat aortas exhibit an ''embryonic growth phenotype'' in
culture ( Cook, C. L., M. C. M. Weiser, P. E. Schwartz, C. L. Jones,
and R. A. Majack. 1994. Circ. Res. 74:189-196). Cells in this growth p
henotype exhibit autonomous, serum-independent replication, in contras
t to SMC in the ''adult'' growth phenotype, whose proliferation in cul
ture is dependent on exogenous mitogens. To determine which of these t
wo phenotypes is genetically dominant, heterokaryons were constructed
between adult and embryonic (day e17) rat aortic SMC. The fused cells
were maintained in serum-free medium for 3 d, then were labeled with b
romodeoxyuridine (BrdU) for an additional 24 h. Under these conditions
, parental e17 SMC exhibited a high rate of self-driven DNA synthesis
(73-85% BrdU-positive cells), while parental adult SMC showed minimal
replication (13-21% BrdU-positive cells). Homokaryons of parental cell
s exhibited parental growth phenotypes and showed the expected mitogen
ic response when stimulated with serum. Heterokaryons between e17 and
adult SMC exhibited a nonautonomous growth phenotype; the ''adult'' gr
owth phenotype was calculated to be dominant in >89% of all true heter
okaryons. The data suggest that adult SMC express molecules capable of
genetically extinguishing or otherwise inhibiting the autonomous repl
ication of embryonic SMC.