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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Jul;86(7):670–676. doi: 10.1111/j.1349-7006.1995.tb02451.x

Stimulatory Effect of Interleukin‐1α on Proliferation through a Ca2+/Calmodulindependent Pathway of a Human Thyroid Carcinoma Cell Line, NIM 1

Nobuo Inokuchi 1,, Kazuya Zeki 1, Isao Morimoto 1, Yoichiro Nakano 1, Takashi Fujihira 1, Uki Yamashita 2, Nobuyuki Yanagihara 3, Futoshi Izumi 3, Sumiya Eto 1
PMCID: PMC5920890  PMID: 7559085

Abstract

NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin‐1α (IL‐1α) and granulocyte‐colony stimulating factor. In the present study, we investigated the signal transduction pathway in the proliferation of NIM 1 cells evoked by IL‐1α. Incubation of NIM 1 cells with IL‐1α for 48 h increased the incorporation of 3H‐thymidine (3H‐TdR). The stimulatory effect of IL‐1α was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL‐1α evoked an influx of 45Ca into NIM 1 cells within 3 min in a concentration‐dependent manner (0.01–1 ng/ml). These stimulatory effects of IL‐1α on both 3H‐TdR incorporation and 45Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage‐dependent Ca2+ channels, in a concentration‐dependent manner (10–1000 nM). The stimulatory effect of IL‐1α on 3H‐TdR incorporation was inhibited by N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalenesulfonamide (W‐7), an antagonist of calmodulin, but not by 1‐(5‐isoquinoline sulfonyl)‐2‐methylpiperazine (H‐7), an inhibitor of protein kinase C. While the culture medium initially contained 0.75 mM Ca2+, inhibition of 3H‐TdR incorporation by nicardipine and W‐7 under these baseline conditions was also recognized. These results suggest that IL‐1α stimulates cell proliferation through a Ca2+/calmodulin‐dependent pathway in NIM 1 cells.

Keywords: Thyroid carcinoma, Interleukin‐1α, Calcium, Calmodulin, Cell proliferation

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