Sex steroid hormones act as growth factors.
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.
Migliaccio
A
A
Dipartimento di Patologia generale-II Università di Napoli, Via L. De Crecchio, 7-I-80138 Naples, Italy.
Castoria
G
G
Di Domenico
M
M
de Falco
A
A
Bilancio
A
A
Lombardi
M
M
Bottero
D
D
Varricchio
L
L
Nanayakkara
M
M
Rotondi
A
A
Auricchio
F
F
D016475:3T3 Cells; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002455:Cell Division; D019938:Cyclin D1 / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D000081247:CSK Tyrosine-Protein Kinase; D019938:Cyclin D1; D004247:DNA; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D012739:Gonadal Steroid Hormones; D006133:Growth Substances; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019061:src-Family Kinases; C000631346:CSK protein, human