Enhancement of the invasive ability of a transformed human bronchial epithelial cell line by 12-o-tetra-decanoyl-phorbol-13-acetate and diacylglycerol

R. Daniel Bonfil, Shigeru Momiki, Rafael Fridman, Reuven Reich, Roger Reddel, Curtis C. Harris, Andres Klien-szanto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The effect of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was studied using an immortalized human bronchial epithelial cell line, BEAS-2B, both in vivo and in vitro. The in vivo model consisted of tracheas reconstituted with an epithelium of BEAS-2B cells xenotransplanted into athymic nude mice. Intraluminal TPA treatment caused increased BEAS-2B cell proliferation and downgrowth into the tracheal stroma. In an in vitro invasion assay, TPA enhanced the invasive capacity of BEAS-2B cells 20- to 25-fold. A similar result was observed with diacylglycerol (DAG), an endogenous activator of protein kinase C, and the effects of TPA and DAG were abolished by simultaneous treatment with H-7, a protein kinase C inhibitor. TPA induced type IV collagenolysis, and this effect also was prevented by H-7. These data are consistent with the hypothesis that TPA causes these cells to become invasive by inducing collagenase activity and that this effect is mediated via protein kinase C.

Original languageEnglish
Pages (from-to)2335-2338
Number of pages4
JournalCarcinogenesis
Volume10
Issue number12
DOIs
StatePublished - Dec 1989
Externally publishedYes

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