Molecular mechanism of a cross-talk between oestrogen and growth factor signalling pathways.
Oestrogen (E2) plays significant roles in variety of biological events such as the development and maintenance of female reproductive organs, bone and lipid metabolisms. More recently, from study of knock-out mice deficient in oestrogen receptor (ER) alpha and ERbeta it turned out that normal spermatogenesis requires the E2 actions. Furthermore, this female steroid hormone is also well known to be deeply involved in many pathophysiological events such as osteoporosis and cancer development in female reproductive organs. It is particularly well known that most breast cancer is dependent on E2 in its development. Such E2 actions are thought to be mediated through two subtypes of ERs. Growth factors have been shown to synergize in this E2 signalling pathway, although the actual molecular mechanism largely remains unknown. Recently, we found that the MAP kinase activated by growth factors phosphorylates the Ser118 residue of the human ERalpha A/B domain and this phosphorylation potentiates the N-terminal transactivation function (AF-1) of human ERalpha, indicating the possible molecular mechanism of a novel cross-talk between E2 and growth factor signalling pathways. More recently, we have identified a coactivator associating with the hERalpha AF-1 in a MAPK-mediated phosphorylation-dependent manner. In this review, the molecular mechanism of this cross-talk is discussed in terms of the transactivation function of ERs, and their coactivators.
Kato
S
S
The Institute of Molecular and Celluar Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. uskato@mail.ecc.u-tokyo.ac.jp
Masuhiro
Y
Y
Watanabe
M
M
Kobayashi
Y
Y
Takeyama
K I
KI
Endoh
H
H
Yanagisawa
J
J
D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008957:Models, Genetic; D020239:Receptor Cross-Talk; D011960:Receptors, Estrogen / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D020928:Mitogen-Activated Protein Kinases