Src-dependent signalling pathway regulation by sex-steroid hormones: therapeutic implications.
Sex-steroid hormones trigger association of their receptors with signalling effectors, and activate complex networks. These effectors include Src and p85alpha, the PI3-kinase (PI3K) regulatory subunit. Remarkably, various hormonal effects, such as DNA synthesis of mammary and prostate cancer cells, vasorelaxation and migration of different cell types are evoked by this activation. In addition, there are reports on a limited but increasing number of cells responding to hormones through signalling activation in the absence of receptor-dependent transcriptional activity. Altogether these findings indicate that further study is required on signalling inhibitors to control progression of tumors expressing steroid receptors. In addition, new molecules interfering in recruitment of signalling effectors by steroid receptors and leaving unaffected the receptor transcriptional activity could be employed to reduce cell proliferation. Inhibitors of steroid receptor-dependent signal transduction might emerge as a new category of steroid receptor antagonists.
Migliaccio
Antimo
A
Dipartimento di Patologia Generale della II Università di Napoli, Via L. De Crecchio 7, 80138 Naples, Italy. antimo.migliaccio@unina2.it
Castoria
Gabriella
G
Auricchio
Ferdinando
F
D002455:Cell Division; D002465:Cell Movement / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D016391:Genes, src / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D015398:Signal Transduction
D012739:Gonadal Steroid Hormones; D019869:Phosphatidylinositol 3-Kinases