✦ LIBER ✦

CCKB/gastrin receptor mediates synergistic stimulation of DNA synthesis and cyclin D1, D3, and E expression in Swiss 3T3 cells

✍ Scribed by Elena Zhukova; James Sinnett-Smith; Helen Wong; Terence Chiu; Enrique Rozengurt

Publisher: John Wiley and Sons
Year: 2001
Tongue: English
Weight: 522 KB
Volume: 189
Category: Article
ISSN: 0021-9541
DOI: 10.1002/jcp.10018

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

In order to develop a model system for identifying signaling pathways and cell cycle events involved in gastrin‐mediated mitogenesis, we have used high efficiency retroviral‐mediated transfection of cholecystokinin (CCK)~B~/gastrin receptor into Swiss 3T3 cells. The retrovirally‐transfected CCK~B~/gastrin receptor binds ^125^I‐CCK‐8 with high affinity (Kd = 1.1 nM) and is functionally coupled to intracellular signaling pathways including rapid and transient increase in Ca^2+^ fluxes, protein kinase C‐dependent protein kinase D activation, and MEK‐dependent ERK1/2 activation. In the presence of insulin, CCK‐8 or gastrin induced a 66.5 ± 8.8‐fold (mean ± SEM, n = 24 in eight independent experiments) increase in cellular DNA synthesis, reaching a level similar to that achieved by stimulation with a saturating concentration of fresh serum, and much greater than the response to each agonist added alone. CCK‐8 also induced a striking increase in the expression of cyclins D1, D3, and E and hyperphosphorylation of Rb acting synergistically with insulin. Similar effects were observed when CCK~B~/gastrin receptor was activated in the presence of EGF or bombesin. Our results demonstrate that activation of CCK~B~/gastrin receptor retrovirally‐transfected into Swiss 3T3 induces a potent synergistic effect on DNA synthesis, accumulation of cyclins D1, D3, and E and hyperphosphorylation of Rb in combination with insulin, EGF, or bombesin. Thus, the CCK~B~/gastrin receptor transfected into Swiss 3T3 cells provides a novel model system to elucidate mitogenic signal transduction pathways and cell cycle events activated via this receptor. © 2001 Wiley‐Liss, Inc.

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