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PI3‐kinase in concert with Src promotes the S‐phase entry of oestradiol‐stimulated MCF‐7 cells
Author(s) -
Castoria Gabriella,
Migliaccio Antimo,
Bilancio Antonio,
Di Domenico Marina,
de Falco Antonietta,
Lombardi Maria,
Fiorentino Roberto,
Varricchio Lilian,
Barone Maria Vittoria,
Auricchio Ferdinando
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.21.6050
Subject(s) - proto oncogene tyrosine protein kinase src , protein kinase b , kinase , ly294002 , microbiology and biotechnology , cyclin dependent kinase 2 , pi3k/akt/mtor pathway , mcf 7 , biology , cancer research , chemistry , phosphorylation , signal transduction , protein kinase a , cancer cell , cancer , human breast , genetics
The p85‐associated phosphatidylinositol (PI) 3‐kinase/Akt pathway mediates the oestradiol‐induced S‐phase entry and cyclin D1 promoter activity in MCF‐7 cells. Experiments with Src, p85α and Akt dominant‐negative forms indicate that in oestradiol‐treated cells these signalling effectors target the cyclin D1 promoter. Oestradiol acutely increases PI3‐kinase and Akt activities in MCF‐7 cells. In NIH 3T3 cells expressing ERα, a dominant‐negative p85 suppresses hormone stimulation of Akt. The Src inhibitor, PP1, prevents hormone stimulation of Akt and PI3‐kinase activities in MCF‐7 cells. In turn, stimulation of Src activity is abolished in ERα‐expressing NIH 3T3 fibroblasts by co‐transfection of the dominant‐negative p85α and in MCF‐7 cells by the PI3‐kinase inhibitor, LY294002. These findings indicate a novel reciprocal cross‐talk between PI3‐kinase and Src. Hormone stimulation of MCF‐7 cells rapidly triggers association of ERα with Src and p85. In vitro these proteins are assembled in a ternary complex with a stronger association than that of the binary complexes composed by the same partners. The ternary complex probably favours hormone activation of Src‐ and PI3‐kinase‐dependent pathways, which converge on cell cycle progression.