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Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Oncogene volume 21, pages 1097–1107 (2002)Cite this article

Abstract

Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of fibulin-1 mRNA results in four different variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of fibulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, fibulin-1C and -1D are the predominant forms, whereas fibulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coamplification of fibulin-1C and -1D to study the relative expression of these fibulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the fibulin-1C:1D and fibulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, fibulin-1C mRNA was induced by estradiol in a dose- and time-dependent manner. Since others and we have previously shown an increased expression of ERα as compared to ERβ in ovarian cancer cells, we investigated whether ERα or ERβ is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and fibulin-1, was infected with recombinant ERα or ERβ encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERα- but not ERβ-infected cells, suggesting that fibulin-1C induction is mediated through ERα. In ovarian tumors, a trend towards a correlation between fibulin-1C and ERα expression levels was noted. In conclusion, this study showed an increased fibulin-1C:-1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This finding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERα promoted ovarian tumor progression.

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Acknowledgements

The authors thank Mrs Marie-Christine Lecq for her careful technical assistance. This work was supported by the ‘Centre Hospitalier Universitaire de Montpellier’ (AOI 7619), the ‘Ligue Nationale de Recherche Contre le Cancer’ and the ‘Institut National de la Santé ´et de la Recherche Médicale’. F Moll is a recipient of a grant from the French ‘Ministère de la Recherche et de la Technologie’.

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Authors and Affiliations

  1. Unité INSERM 540, 60 rue de Navacelles, 34095 Montpellier, France

    Frederic Moll, Gwendal Lazennec, Pascal Roger, Dany Chalbos, Thierry Maudelonde, Henri Rochefort & Pascal Pujol

  2. Department of Obstetrics and Gynecology, via Ventimiglia 3, 10126, Turin, Italy

    Dionyssios Katsaros

  3. Services de Biologie Cellulaire et Hormonale et de Hôpital Arnaud de Villeneuve, 34295, Montpellier, France

    Nicolas Hellio, Thierry Maudelonde, Henri Rochefort & Pascal Pujol

  4. Gynécologie-Obstétrique, Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, 34295, Montpellier, France

    Pierre-Ludovic Giacalone

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  1. Frederic Moll
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  2. Dionyssios Katsaros
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Correspondence to Pascal Pujol.

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Moll, F., Katsaros, D., Lazennec, G. et al. Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells. Oncogene 21, 1097–1107 (2002). https://doi.org/10.1038/sj.onc.1205171

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  • DOI: https://doi.org/10.1038/sj.onc.1205171

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