Transcriptional and Posttranscriptional regulation of fibulin-1 by estrogens leads to differential induction of messenger ribonucleic acid variants in ovarian and breast cancer cells

被引:48
作者
Bardin, A
Moll, F
Margueron, R
Delfour, C
Chu, ML
Maudelonde, T
Cavailles, V
Pujol, P
机构
[1] CHU Montpellier, Hop Arnaud Villeneuve, INSERM, U540, F-34095 Montpellier, France
[2] CHU Montpellier, Hop Arnaud Villeneuve, Serv Biol Cellulaire & Hormonale, F-34095 Montpellier, France
[3] Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA
关键词
D O I
10.1210/en.2004-1239
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fibulin-1 is an extracellular matrix protein overexpressed in epithelial ovarian and breast cancers. In estrogen receptor (ER)-positive ovarian and breast cancer cell lines, fibulin-1 mRNA levels are markedly increased by estrogens. Transfection experiments using fibulin-1 promoter constructs indicate that 17beta-estradiol (E2) increases fibulin-1 gene transcription and that ERalpha is more potent than ERbeta to mediate E2 regulation of the transfected fibulin-1 promoter. Using SL2 cells devoid of specificity protein 1 (Sp1) and site-directed mutagenesis of GC boxes, we evidenced that the E2 regulation occurs through a proximal specificity protein 1 binding site. In addition, we show that fibulin-1C and -1D mRNAs, the two major fibulin-1 splicing variants, are differentially induced by E2. The induction of both mRNAs variants is direct and independent of a newly synthesized protein intermediate. Interestingly, actinomycin D chase experiments demonstrate that E2 treatment selectively shortens the fibulin-1D mRNA half-life. This indicates that estrogens affect differentially the stability of fibulin-1 variants and may explain the lower accumulation of fibulin-1D mRNA on E2 treatment. In conclusion, our data show that estrogens, via ERalpha, are key regulators of fibulin-1 expression at both the transcriptional and post-transcriptional levels. The preferential induction of the fibulin-1C variant, which is overexpressed in ovarian and breast cancer, might play an important role in estrogen-promoted carcinogenesis.
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页码:760 / 768
页数:9
相关论文
共 65 条
[1]   Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures - The Women's Health Initiative randomized trial [J].
Anderson, GL ;
Judd, HL ;
Kaunitz, AM ;
Barad, DH ;
Beresford, SAA ;
Pettinger, M ;
Liu, J ;
McNeeley, SG ;
Lopez, AM .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 290 (13) :1739-1748
[2]   A+U-rich-element RNA-binding factor 1/heterogeneous nuclear ribonucleoprotein D gene expression is regulated by oestrogen in the rat uterus [J].
Arao, Y ;
Kikuchi, A ;
Ikeda, K ;
Nomoto, S ;
Horiguchi, H ;
Kayama, F .
BIOCHEMICAL JOURNAL, 2002, 361 :125-132
[3]   FIBULIN IS AN EXTRACELLULAR-MATRIX AND PLASMA GLYCOPROTEIN WITH REPEATED DOMAIN-STRUCTURE [J].
ARGRAVES, WS ;
TRAN, H ;
BURGESS, WH ;
DICKERSON, K .
JOURNAL OF CELL BIOLOGY, 1990, 111 (06) :3155-3164
[4]   FIBULIN, A NOVEL PROTEIN THAT INTERACTS WITH THE FIBRONECTIN RECEPTOR-BETA SUBUNIT CYTOPLASMIC DOMAIN [J].
ARGRAVES, WS ;
DICKERSON, K ;
BURGESS, WH ;
RUOSLAHTI, E .
CELL, 1989, 58 (04) :623-629
[5]   Coordinate regulation of transcription and splicing by steroid receptor coregulators [J].
Auboeuf, D ;
Hönig, A ;
Berget, SM ;
O'Malley, BW .
SCIENCE, 2002, 298 (5592) :416-419
[6]  
Baldwin WS, 1998, IN VITRO CELL DEV-AN, V34, P649
[7]  
Beral Valerie, 2003, Lancet, V362, P419, DOI 10.1016/S0140-6736(03)14065-2
[8]   MITHRAMYCIN INHIBITS SP1 BINDING AND SELECTIVELY INHIBITS TRANSCRIPTIONAL ACTIVITY OF THE DIHYDROFOLATE-REDUCTASE GENE INVITRO AND INVIVO [J].
BLUME, SW ;
SNYDER, RC ;
RAY, R ;
THOMAS, S ;
KOLLER, CA ;
MILLER, DM .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 88 (05) :1613-1621
[10]   Latent transforming growth factor β-binding protein-3 and fibulin-1C interact with the extracellular domain of the heparin-binding EGF-like growth factor precursor -: art. no. 2 [J].
Brooke, JS ;
Cha, JH ;
Eidels, L .
BMC CELL BIOLOGY, 2002, 3 (1)