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

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 posttranscriptional 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.

[1]  A. Folsom,et al.  Estrogen Replacement Therapy and Ovarian Cancer , 2004, Epidemiology.

[2]  S. Ménard,et al.  Identification of Breast Cancer-Restricted Antigens by Antibody Screening of SKBR3 cDNA Library Using a Preselected Patient's Serum , 2002, Breast Cancer Research and Treatment.

[3]  Ana Maria Lopez,et al.  Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. , 2003, JAMA.

[4]  Valerie Beral,et al.  Breast cancer and hormone-replacement therapy in the Million Women Study , 2003, The Lancet.

[5]  R. Langer,et al.  Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women's Health Initiative Randomized Trial , 2003 .

[6]  G. Stoecklin,et al.  A novel mechanism of tumor suppression by destabilizing AU-rich growth factor mRNA , 2003, Oncogene.

[7]  Virginie Copois,et al.  Assessment of RNA Quality Extracted from Laser-Captured Tissues Using Miniaturized Capillary Electrophoresis , 2003, Laboratory Investigation.

[8]  M. Duffy,et al.  Elevated expression and altered processing of fibulin-1 protein in human breast cancer , 2003, British Journal of Cancer.

[9]  Bert W O'Malley,et al.  Coordinate Regulation of Transcription and Splicing by Steroid Receptor Coregulators , 2002, Science.

[10]  Jason J Chen,et al.  Interaction of oncogenic papillomavirus E6 proteins with fibulin-1. , 2002, Biochemical and biophysical research communications.

[11]  Heidi D Nelson,et al.  Postmenopausal hormone replacement therapy: scientific review. , 2002, JAMA.

[12]  P. Hartge,et al.  Menopausal hormone replacement therapy and risk of ovarian cancer. , 2002, JAMA.

[13]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[14]  Warren N Ratna,et al.  The upstream stem–loop domain of the 3′ untranslated region of apolipoprotein II mRNA binds the estrogen-regulated mRNA stabilizing factor , 2002, The Journal of Steroid Biochemistry and Molecular Biology.

[15]  A. Kornblihtt,et al.  Alternative splicing: multiple control mechanisms and involvement in human disease. , 2002, Trends in genetics : TIG.

[16]  M. Castoldi,et al.  Structural and functional characterization of the human and mouse fibulin-1 gene promoters: role of Sp1 and Sp3. , 2002, The Biochemical journal.

[17]  D. Katsaros,et al.  Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells , 2002, Oncogene.

[18]  W. V. D. Van de Ven,et al.  The fibulin-1 gene (FBLN1) is disrupted in a t(12;22) associated with a complex type of synpolydactyly , 2002, Journal of medical genetics.

[19]  K. Ikeda,et al.  A+U-rich-element RNA-binding factor 1/heterogeneous nuclear ribonucleoprotein D gene expression is regulated by oestrogen in the rat uterus. , 2002, The Biochemical journal.

[20]  Joanna S Brooke,et al.  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 , 2002, BMC Cell Biology.

[21]  A. Czirók,et al.  Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility. , 2001, Journal of cell science.

[22]  R. Timpl,et al.  Glucocorticoids down‐regulate the extracellular matrix proteins fibronectin, fibulin‐1 and fibulin‐2 in bone marrow stroma , 2001, European journal of haematology.

[23]  M. Thun,et al.  Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. , 2001, JAMA.

[24]  S. Kohsaka,et al.  Fibulin‐1 binds the amino‐terminal head of β‐amyloid precursor protein and modulates its physiological function , 2001 .

[25]  S. Safe.  Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions. , 2001, Vitamins and hormones.

[26]  S. Coughlin,et al.  A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer. , 2000, Journal of clinical epidemiology.

[27]  P. Blackshear,et al.  Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability. , 2000, Blood.

[28]  Eva Enmark,et al.  Ligand-, Cell-, and Estrogen Receptor Subtype (α/β)-dependent Activation at GC-rich (Sp1) Promoter Elements* , 2000, The Journal of Biological Chemistry.

[29]  P. Blackshear,et al.  Necrosis Factor Alpha Mrna Deadenylation and Destabilization of Tumor Au-rich Elements and Promotes the Evidence That Tristetraprolin Binds To , 1999 .

[30]  B He,et al.  The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  P. Pujol,et al.  Increased immunostaining of fibulin-1, an estrogen-regulated protein in the stroma of human ovarian epithelial tumors. , 1998, The American journal of pathology.

[32]  H. Rochefort,et al.  Estradiol and fibulin‐1 inhibit motility of human ovarian‐ and breast‐cancer cells induced by fibronectin , 1998, International journal of cancer.

[33]  S. Safe,et al.  Functional synergy between the transcription factor Sp1 and the estrogen receptor. , 1997, Molecular endocrinology.

[34]  J. Mccormick,et al.  Suppression of anchorage-independent growth and matrigel invasion and delayed tumor formation by elevated expression of fibulin-1D in human fibrosarcoma-derived cell lines , 1997, Oncogene.

[35]  W. Wahli,et al.  Functional Interactions between the Estrogen Receptor and the Transcription Activator Sp1 Regulate the Estrogen-dependent Transcriptional Activity of the Vitellogenin A1 ioPromoter* , 1997, The Journal of Biological Chemistry.

[36]  R. Dodson,et al.  Vigilin, a Ubiquitous Protein with 14 K Homology Domains, Is the Estrogen-inducible Vitellogenin mRNA 3′-Untranslated Region-binding Protein* , 1997, The Journal of Biological Chemistry.

[37]  M. Mattei,et al.  Human fibulin-1D: molecular cloning, expression and similarity with S1-5 protein, a new member of the fibulin gene family. , 1997, Matrix biology : journal of the International Society for Matrix Biology.

[38]  N. Copeland,et al.  Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. , 1997, Molecular endocrinology.

[39]  J. Barrett,et al.  BG-1 ovarian cell line: An alternative model for examining estrogen-dependent growth in vitro , 1998, In Vitro Cellular & Developmental Biology - Animal.

[40]  J. Polman,et al.  ERβ: Identification and characterization of a novel human estrogen receptor , 1996 .

[41]  J. Gustafsson,et al.  Cloning of a novel receptor expressed in rat prostate and ovary. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[42]  H. Rochefort,et al.  Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  C. Y. Chen,et al.  AU-rich elements: characterization and importance in mRNA degradation. , 1995, Trends in biochemical sciences.

[44]  P. Webb,et al.  Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. , 1995, Molecular endocrinology.

[45]  T. Sasaki,et al.  Structural characterization of two variants of fibulin-1 that differ in nidogen affinity. , 1995, Journal of molecular biology.

[46]  F. Bresciani,et al.  Identification of a specific pattern of "immediate-early" gene activation induced by estrogen during mitogenic stimulation of rat uterine cells. , 1993, Receptor.

[47]  M. Pike,et al.  Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. , 1993, Epidemiologic reviews.

[48]  T. Maudelonde,et al.  Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1. , 1992, The Journal of clinical endocrinology and metabolism.

[49]  C. Koller,et al.  Mithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo. , 1991, The Journal of clinical investigation.

[50]  R. Pastori,et al.  Estrogen-induced ribonuclease activity in Xenopus liver. , 1991, Biochemistry.

[51]  G. Brewer,et al.  An A + U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro , 1991, Molecular and cellular biology.

[52]  B. Varnum,et al.  The TIS11 primary response gene is a member of a gene family that encodes proteins with a highly conserved sequence containing an unusual Cys-His repeat , 1991, Molecular and cellular biology.

[53]  M. Somerman,et al.  Fibulin is an extracellular matrix and plasma glycoprotein with repeated domain structure , 1990, The Journal of cell biology.

[54]  E. Ruoslahti,et al.  Fibulin, a novel protein that interacts with the fibronectin receptor β subunit cytoplasmic domain , 1989, Cell.

[55]  K. Geisinger,et al.  Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors , 1989, Cancer.

[56]  V. Sukhatme,et al.  Nucleotide sequence of a cDNA encoding TIS11, a message induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate. , 1989, Oncogene.

[57]  R. Tjian,et al.  Analysis of Sp1 in vivo reveals mutiple transcriptional domains, including a novel glutamine-rich activation motif , 1988, Cell.

[58]  C. Benz,et al.  Estrogen-induced post-transcriptional modulation of c-myc proto-oncogene expression in human breast cancer cells. , 1988, The Journal of biological chemistry.

[59]  B. Henderson,et al.  Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. , 1988, Cancer research.

[60]  P. Argos,et al.  Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A , 1986, Nature.

[61]  D. Chalbos,et al.  Cloning of cDNA sequences of a progestin-regulated mRNA from MCF7 human breast cancer cells. , 1986, Nucleic acids research.

[62]  R. Scully,et al.  Ovarian metastases from cancer of the lung: problems in interpretation--a report of seven cases. , 1985, Gynecologic oncology.

[63]  H. Rochefort,et al.  Estrogen-induced proteins in human breast cancer cells. , 1984, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.