Abstract
Tumor promoters, such as phorbol myristate acetate (PMA), facilitate carcinogenesis by mechanisms that may involve changes in intracellular Ca2+ metabolism and distribution of Ca2+, as well as activation of a Ca2+-and phospholipid-dependent protein kinase, referred to as protein kinase C. We compared the actions of PMA on GH3 cloned pituitary cells with those of thyrotropin releasing hormone (TRH), an established Ca2+-mobilizing agent. The TRH treatment produced a45Ca efflux, inhibited45Ca uptake, diminished chlortetracycline fluorescence, and stimulated cAMP accumulation and protein synthesis in a Ca2+-dependent manner. Like TRH, PMA produced an efflux of45Ca and inhibited45Ca uptake; however, the phorbol ester stimulated cAMP accumulation and protein synthesis in the absence of external calcium and failed to alter chlortetracycline fluorescence. The TMB-8, a putative inhibitor of the mobilization of membrane-associated Ca2+, did not alter PMA-induced stimulation of protein synthesis.
The results suggest that PMA-induced changes in Ca2+ metabolism are not caused by the mobilization of membrane-associated calcium. Alternative proposals are that PMA (1) inhibits Ca2+ influx and/or (2) mobilizes calcium from nonmembranous storage sites. Further study is needed to characterize the mechanism through which tumor-promoting phorbol esters influence Ca2+ metabolism and to ascertain the significance of changes in Ca2+ metabolism to cellular processes affected by these substances.
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Boyer, I.J., Brostrom, M.A. Actions of a tumor-promoting phorbol ester in a cloned rat pituitary cell. Biol Trace Elem Res 13, 291–292 (1987). https://doi.org/10.1007/BF02796640
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DOI: https://doi.org/10.1007/BF02796640