Sex steroid hormones act as growth factors

• Published in: Journal of steroid biochemistry and molecular biology 2002-12, Vol.83 (1), p.31-35
• Main Authors: Migliaccio, A., Castoria, G., Di Domenico, M., de Falco, A., Bilancio, A., Lombardi, M., Bottero, D., Varricchio, L., Nanayakkara, M., Rotondi, A., Auricchio, F.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Biological and medical sciences; Cell Division; Cos cells; Cyclin D1 - metabolism; DNA - biosynthesis; Estradiol - metabolism; Estradiol - pharmacology; Estrogen Receptor Modulators - pharmacology; Fundamental and applied biological sciences. Psychology; Gonadal Steroid Hormones - metabolism; Growth Substances - metabolism; Humans; Mice; Phosphatidylinositol 3-Kinases - metabolism; PI3-kinase; Protein-Tyrosine Kinases - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Sex steroid hormones; Signal Transduction; src-Family Kinases; Steroid hormones. Cholecalciferol derivatives; Time Factors; Transcription, Genetic; Transcriptional Activation; Tumor Cells, Cultured; Vertebrates: endocrinology
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(02)00264-9

We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of cell lines derived from human mammary or prostate cancers. In addition, hormone-dependent pathway activation can be induced in Cos cells, upon transfection of classic steroid receptors. Cross-talks between sex steroid receptors regulate their association with Src and consequent pathway activation. Oestradiol treatment of MCF-7 cells triggers simultaneous association of ER with Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase (PI3-kinase) and activation of Src- and PI3-K-dependent pathways. Activation of the latter pathway triggers cyclin D1 transcription, that is unaffected by Mek-1 activation. This suggests that simultaneous activation of different signalling effectors is required to target different cell cycle components. Thus, a novel reciprocal cross-talk between the two pathways appears to be mediated by the ER. In all tested cells, activation of the signalling pathways has a proliferative role. Transcriptionally inactive ER expressed in NIH 3T3 cells responds to hormone causing Src/Ras/Erk pathway activation and DNA synthesis. This suggests that in these cells genomic activity is required for later events of cell growth.