Nb2 rat lymphoma cells are dependent on prolactin (PRL) for growth. Me
mbrane lipid composition of Nb2 cells undergoes rapid modification whe
n these cells are grown in culture media supplemented with specific fa
tty acids. Since the actions of PRL are mediated through specific memb
rane receptors, the following studies were conducted to characterize t
he lipid-dependent events involved in fatty acid modulation of PRL-ind
uced cell proliferation. Nb2 cells were grown in suspension cultures i
n control or fatty acid-supplemented media, in the presence of various
doses of PRL. PRL-induced cell growth was significantly enhanced by a
rachidonate, but significantly attenuated by stearate supplementation
of the culture media. A direct relationship was observed between the c
oncentration of specific fatty acid added to the culture media and the
magnitude with which this fatty acid was incorporated into Nb2 cell m
embranes, as determined by gas chromatography. Acute treatment with ph
orbol ester enhanced Nb2 cell growth in control media and reversed the
attenuating effects of membrane stearic acid enrichment. However, PRL
-induced Nb2 cell growth was similar with or without the presence of p
horbol ester, when cells were grown in media supplemented with arachid
onate. Addition of protein kinase C (PKC) inhibitors to control and fa
tty acid-supplemented media resulted in a dose-dependent inhibition of
PRL-indUced Nb2 cell proliferation. These results suggest that lipid
modulation of Nb2 mitogenic-responsiveness to PRL is mediated through
alterations in PKC activation.