Open AccessTumor-promoter-resistant cells lack trisialoganglioside response.
Author(s) -
Leela Srinivas,
Thomas D. Gindhart,
Nancy H. Colburn
Publication year - 1982
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.79.16.4988
Subject(s) - tumor promotion , phorbol , phenotype , receptor , cell culture , biology , transformation (genetics) , cell , microbiology and biotechnology , tetradecanoylphorbol acetate , biochemistry , chemistry , gene , signal transduction , protein kinase c , genetics , carcinogenesis
JB6 mouse epidermal cells shift irreversibly to tumor cell phenotype (anchorage independence and tumorigenicity) on treatment with phorbol esters and other tumor promoters. Exposure to phorbol 12-myristate 13-acetate (PMA) decreased the de novo synthesis of trisialoganglioside (GT) in these "promotable" JB6 cells to 5-10% of that of untreated cells. The GT decrease occurred consistently in promotion-sensitive cells and not in promotion-resistant variants. Insertion of GT into membranes of PMA-treated cells inhibited PMA promotion of transformation as measured by agar colony induction. This ability to inhibit promotion of transformation is specific to GT and is not shared by other sialoglycoconjugates, including gangliosides GM1, GD1a, and asialo-GM1. The mechanism of the blocking activity of GT must be distal to the binding of PMA to its receptors, as exogenously added GT does not inhibit specific binding of tritiated phorbol diester. GT is unable to block agar colony formation by transformed cell lines, showing that its level of action is at induction of the transformed phenotype rather than at expression of it.