TY - JOUR
T1 - Activation of adenosine deaminase in MCF-7 cells through IGF-estrogen receptor α crosstalk
AU - Xie, W.
AU - Duan, R.
AU - Safe, S. H.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Adenosine deaminase (ADA) regulates cellular levels of adenosine and deoxyadenosine, and 17β-estradiol (E2) induces ADA mRNA in MCF-7 human breast cancer cells. IGF-I also induces ADA gene expression in these cells, and induction of this response through IGF activation of estrogen receptor α (ERα) was further investigated. IGF and other polypeptide growth factors induce reporter gene expression in MCF-7 cells contransfected with ERα expression plasmid and pADA211, a construct containing the - 211 to +11 region of the ADA gene promoter which is required for high basal and E2-inducible activity. Deletion analysis of this promoter demonstrates that IGF activates ERα/Sp1 interactions with multiple GC-rich sites in the promoter and this response is abrogated in cells transfected with ERα containing mutations at Ser118 or Ser163. IGF induces both MAPK (mitogen-activated protein kinase) and P13-K (phosphatidylinositol-3-kinase) phosphorylation cascades in MCF-7 cells; however, using a series of inhibitors and dominant negative constructs, our results show that induction of ADA by IGF activation of ERα/Sp1 is dependent on the MAPK signaling pathway.
AB - Adenosine deaminase (ADA) regulates cellular levels of adenosine and deoxyadenosine, and 17β-estradiol (E2) induces ADA mRNA in MCF-7 human breast cancer cells. IGF-I also induces ADA gene expression in these cells, and induction of this response through IGF activation of estrogen receptor α (ERα) was further investigated. IGF and other polypeptide growth factors induce reporter gene expression in MCF-7 cells contransfected with ERα expression plasmid and pADA211, a construct containing the - 211 to +11 region of the ADA gene promoter which is required for high basal and E2-inducible activity. Deletion analysis of this promoter demonstrates that IGF activates ERα/Sp1 interactions with multiple GC-rich sites in the promoter and this response is abrogated in cells transfected with ERα containing mutations at Ser118 or Ser163. IGF induces both MAPK (mitogen-activated protein kinase) and P13-K (phosphatidylinositol-3-kinase) phosphorylation cascades in MCF-7 cells; however, using a series of inhibitors and dominant negative constructs, our results show that induction of ADA by IGF activation of ERα/Sp1 is dependent on the MAPK signaling pathway.
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U2 - 10.1677/jme.0.0260217
DO - 10.1677/jme.0.0260217
M3 - Article
C2 - 11357058
AN - SCOPUS:0034993857
VL - 26
SP - 217
EP - 228
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
SN - 0952-5041
IS - 3
ER -