PMID: 2496916May 15, 1989Paper

Possible involvement of Ca2+ mobilization and protein kinase C activation in the induction of spontaneous metastasis by mouse mammary adenocarcinoma cells

Cancer Research
B KorczakR S Kerbel

Abstract

Evidence is provided to show that two secondary cell-signaling pathways, Ca2+ mobilization and the activation of protein kinase C (PKC), are involved in the induction of spontaneous metastasis in mouse adenocarcinoma cell line SP1. Unlike the parental cells, which were found to be tumorigenic but unable to metastasize from a s.c. site, SP1 cells treated with ionophore A23187 (to mobilize Ca2+) or phorbol 12-myristate 13-acetate (to activate PKC) were able to metastasize spontaneously. Analysis of SP1 cells treated with either agent separately or with both agents simultaneously revealed that both pathways contributed to the final response in a separate and nonsynergistic way. The induced metastatic phenotype in most cases appeared to be heritable. Examination of Ca2+ sources during cell activation by ionophore A23187 suggested that internal Ca2+ was sufficient for the process of induction. Examination of PKC activity and its intracellular distribution during and after treatment of SP1 cells with ionophore A23187 and phorbol 12-myristate 13-acetate were also evaluated. The results suggested that the basal levels of PKC and the activation of the enzyme appear to be involved in the induction of spontaneous metastasis. Taken togethe...Continue Reading

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