RT info:eu-repo/semantics/article
T1 The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock Factor-1 and activator protein-1 transcription factors
A1 Bayón Prieto, Yolanda
A1 Ortiz, Maria A.
A1 Lopez Hernandez, Francisco J.
A1 Howe, Philip H.
A1 Piedrafita, F. Javier
K1 Retinoids
K1 Retinoides
K1 Cáncer
K1 24 Ciencias de la Vida
AB Retinoids mediate numerous biological responses through the transcriptional activation of nuclear retinoid receptors. Due to their antiproliferative activity, retinoids have shown promise as anticancer agents. Synthetic analogs have been described that selectively activate one subset of the retinoid receptors or inhibit their transcriptional activity. Some of these compounds exhibit strong anticancer activity, which is associated with their ability to induce apoptosis. Here we describe that the retinoid antagonist MX781 causes a substantial increase of clusterin mRNA and protein levels in prostate carcinoma cells. In contrast, retinoic acid and other synthetic agonists and antagonists show no effect on clusterin mRNA/protein levels. Induction of clusterin mRNA is associated with transcriptional activation of the clusterin promoter, which requires the proximal -218-bp region containing binding sites for heat shock factor (HSF)-1, activator protein (AP)-2, and AP-1 transcription factors. MX781 slightly induces AP-1 DNA binding activity, and mutation of the AP-1 site differentially affects the activation of the clusterin promoter in a cell type-specific manner. In contrast, a robust increase of HSF-1 DNA binding activity is observed in all cancer cell lines examined, and mutation of the heat shock element site in the clusterin promoter completely abolishes MX781-induced transcriptional activation in PC3 and DU145 cells. Other agonist retinoid-related molecules also induce AP-1 activity, but not HSF-1, and elicit no effect on clusterin expression levels. These data point to HSF-1 as an important factor regulating clusterin expression in response to MX781, although AP-1 activity may also participate in a cell type-specific manner.
PB American Association for Cancer Research
SN 0008-5472
YR 2004
FD 2004
LK https://uvadoc.uva.es/handle/10324/47497
UL https://uvadoc.uva.es/handle/10324/47497
LA eng
NO Cancer Research, 2004, vol. 64, n. 16, p. 5905-5912
NO Producción Científica
DS UVaDOC
RD 30-may-2024