Growth and protein phosphorylation in the Nb2 lymphoma: Effect of prolactin, cAMP, and agents that activate adenylate cyclase

Abstract

The Nb2 T lymphoma is unique in that these lymphocytes proliferate in response to prolactin as well as in response to interleukin-2. In this study, we have examined the responsiveness of the adenylate cyclase system in Nb2 cells and the role of this signaling system in regulating proliferation and protein phosphorylation. An analog of cAMP inhibited prolactin-stimulated proliferation and blocked a prolactin-induced decrease in protein phosphorylation. Forskolin, a potent activator of adenylate cyclase in T lymphocytes, did not elevate cAMP levels in Nb2 cells and was not an effective inhibitor of prolactin-induced proliferation. In fact, one preparation of forskolin stimulated proliferation of quiescent Nb2 cells. Like forskolin, prostaglandin E2 did not stimulate cAMP production in Nb2 cells even though it increased cAMP in a preparation of rat peripheral blood lymphocytes. Cholera toxin appeared to ADP-ribosylate a stimulatory guanine nucleotide-binding protein in Nb2 cells, but the toxin did not increase intracellular levels of cAMP nor was it a potent anti-mitogenic agent. Pertussis toxin, an agent that can increase cAMP production through suppression of the inhibitory guanine nucleotide-binding protein, exerted only minor anti-proliferative actions on prolactin-stimulated Nb2 cells. These data suggest that cAMP inhibits Nb2 cell proliferation and prolactin-induced changes in protein phosphorylation but that the adenylate cyclase system in our clone of Nb2 cells responds poorly to agents that normally increase cAMP.

Adenosine induces cell‐cycle arrest and apoptosis in androgen‐dependent and ‐independent prostate cancer cell lines, LNcap‐FGC‐10, DU‐145, and PC3

“…Earlier studies have suggested that an adenylyl cyclase mediated accumulation of intracellular cAMP is the cause of adenosine‐induced cytotoxicity 67–70. In contrast, the viability of DU‐145, PC3, and LNcap prostate cancer cells was not affected by the activation of adenylyl cyclase by forskolin or by the addition of RO‐17721 (as phosphodiestrase inhibitor that increase cAMP).…”