Regulation of murine plasmacytoma transferrin receptor expression and G₁ traversal by plasmacytoma cell growthfactor

Abstract

Many plasmacytomas arising in BALB/c mice require a specific, macrophage-derived growth factor in order to proliferate in vitro. Since transferrin receptor expression is normally regulated by tissue-specific growth factors and because expression of these receptors is required for cell proliferation, we examined the interaction of plasmacytoma growth factor (PCT-GF) on transferrin receptor expression and cell cycle progression in several PCT-GF-dependent and independent plasmacytoma cell lines maintained in vitro. We found that removal of PCT-GF results in a rapid and specific loss of transferrin receptor expression with concomitant G1 arrest in early G1. The time required for G1 arrest to become maximal correlates closely to the initial level of surface transferrin receptor expression and the rate of decay following removal of PCT-GF. The calcium channel blocker diltiazem interferes with the ability of PCT-GF to maintain transferrin receptor expression in PCT-GF-dependent cell lines and causes a G1 arrest of the cell population. When added to a PCT-GF-independent cell line, diltiazem also inhibited transferrin receptor expression and caused G1 arrest. Thus, both PCT-GF-dependent and -independent plasmacytoma cell lines require transferrin receptor expression for growth. In factor dependent cell lines, transferrin receptor expression requires exogenous PCT-GF, while in factor-independent cells, transferrin receptor expression is constitutive. In both cell types, intracellular calcium levels may play a role in receptor expression.

Regulation of Transferrin Receptor Expression and Control of Cell Growth

“…Although the 3 plasmacy toma lines examined took from 16 to 48 h to maximally synchronize in G|, they each took the same amount of time to return to S phase following readdition of IL-6 ( fig. 3), supporting the concept that, whatever the partic ular steady-state level of surface transferrin receptor expression, a uniform, low level receptor number can support growth [5].…”

“…How ever, the majority of these cells are dependent on IL-6 for growth. We have characterized the relationship in these cells between IL-6 and transferrin receptor expres sion and have found that, analogous to the IL-2 depen dence of receptor expression in T cells, in IL-6-dependent plasmacytomas transferrin receptor expression re quires the presence of IL-6 [5], Removal of this growth factor leads to a rapid arrest of cells in the Gi phase of the cell cycle and a concomitant loss of transferrin recep tor expression. The time required for G| arrest to be come maximal correlates closely to the initial level of surface transferrin receptors and its rate of decay follow ing removal of IL-6 ( fig.…”

“…receptor expression from growth factor control. For ex ample, transferrin receptor expression on IL-6-independent plasmacytoma cell lines is on the average 3-fold higer than on their IL-6-dependent counterparts and is not affected by either addition of exogenous IL-6 or removal of any endogenously produced IL-6 with anti-IL-6 antibodies [5,and R.P. Nordan,pers.…”

“…In the inset is the correlation between initial level of surface transferrin receptor expression and time required to reach maximal G* synchrony in the 3 IL-6-dependent cell lines. (From Neckers and Nordan [5], with permission.) receptor expression from growth factor control.…”

An Acute Phase Response Factor/NF-κB Site Downstream of the junB Gene That Mediates Responsiveness to Interleukin-6 in a Murine Plasmacytoma

“…IL-6-dependent 1 cell lines can be established from early transplant generations of these tumors if IL-6 is included in the culture medium (3). In the absence of IL-6, these cell lines arrest in the G 1 phase of the cell cycle and eventually die (4). One such line, T1165, dies within 24 h in the absence of IL-6 but re-enters the S phase in 8 -10 h if restimulated before cell death.…”