TY - JOUR
T1 - pS2 gene expression in HepG2 cells
T2 - Complex regulation through crosstalk between the estrogen receptor α, an estrogen-responsive element, and the activator protein 1 response element
AU - Barkhem, Tomas
AU - Haldosén, Lars Arne
AU - Gustafsson, Jan Åke
AU - Nilsson, Stefan
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - The pS2 promoter is complex with binding sites for a number of protein factors that may participate in modulating its activity. The pS2 gene was transcriptionally activated by estrogens in HepG2 cells transformed (HepER3) to express the estrogen receptor α (ERα). The phorbol ester phorbol 12-myristate 13-acetate (PMA) stimulated pS2 expression in both HepER3 and the parental, non-ER-expressing HepG2 cells, although its activity was substantially less in HepG2 cells. The use of selective protein kinase inhibitors suggested that the MAPK pathway contributes substantially to estrogen stimulation of the pS2 promoter. The activator protein 1 (AP1) site at -332 to -338 in the pS2 promoter had a dominant role in the response to both estrogens and PMA, although the estrogen response element at -393 to -405 was essential to mediate the response to estrogen. The potentiation of pS2 promoter activity by the AP1 motif in response to estrogen was dependent on the ligand binding domain of ERα. Furthermore, the presence of an intact AP1 element in the pS2 promoter sustained suppression of pS2 promoter activity by an LXXLL peptide. In summary, the data suggest that the effect of estrogen is mediated through a cross-talk between the estrogen -respon sive element and the AP1 response element and that ERα plays a crucial role in mediating the effect of both estrogen and PMA.
AB - The pS2 promoter is complex with binding sites for a number of protein factors that may participate in modulating its activity. The pS2 gene was transcriptionally activated by estrogens in HepG2 cells transformed (HepER3) to express the estrogen receptor α (ERα). The phorbol ester phorbol 12-myristate 13-acetate (PMA) stimulated pS2 expression in both HepER3 and the parental, non-ER-expressing HepG2 cells, although its activity was substantially less in HepG2 cells. The use of selective protein kinase inhibitors suggested that the MAPK pathway contributes substantially to estrogen stimulation of the pS2 promoter. The activator protein 1 (AP1) site at -332 to -338 in the pS2 promoter had a dominant role in the response to both estrogens and PMA, although the estrogen response element at -393 to -405 was essential to mediate the response to estrogen. The potentiation of pS2 promoter activity by the AP1 motif in response to estrogen was dependent on the ligand binding domain of ERα. Furthermore, the presence of an intact AP1 element in the pS2 promoter sustained suppression of pS2 promoter activity by an LXXLL peptide. In summary, the data suggest that the effect of estrogen is mediated through a cross-talk between the estrogen -respon sive element and the AP1 response element and that ERα plays a crucial role in mediating the effect of both estrogen and PMA.
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U2 - 10.1016/s0026-895x(24)12085-8
DO - 10.1016/s0026-895x(24)12085-8
M3 - Article
C2 - 12021387
AN - SCOPUS:0036262430
SN - 0026-895X
VL - 61
SP - 1273
EP - 1283
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 6
ER -