Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer
<p>Abstract</p> <p>Background</p> <p>Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an int...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-10-01
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| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/8/1/83 |
| _version_ | 1818964581451563008 |
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| author | Fernandez Hervé Biola-Vidamment Armelle Pallardy Marc Emilie Dominique Touboul Cyril Gaudin Françoise Redjimi Nassima Prévot Sophie Balabanian Karl Machelon Véronique |
| author_facet | Fernandez Hervé Biola-Vidamment Armelle Pallardy Marc Emilie Dominique Touboul Cyril Gaudin Françoise Redjimi Nassima Prévot Sophie Balabanian Karl Machelon Véronique |
| author_sort | Fernandez Hervé |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation.</p> <p>Results</p> <p>GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, <it>P </it>< 0.00001, r = 0.56). They were also higher in tumor cells containing large amounts of phosphorylated protein kinase B (p-AKT) (unpaired t test, <it>P </it>< 0.0001). To assess the effect of GILZ on proliferation and AKT activation, we used the BG-1 cell line derived from ovarian tumor cells as a cellular model. GILZ expression was either enhanced by stable transfection or decreased by the use of small interfering (si) RNA targeting GILZ. We found that GILZ increased cell proliferation, phospho-AKT cellular content and AKT kinase activity. Further, GILZ upregulated cyclin D1 and phosphorylated retinoblastoma (p-Rb), downregulated cyclin-dependent kinase inhibitor p21, and promoted the entry into S phase of cell cycle.</p> <p>Conclusion</p> <p>The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.</p> |
| first_indexed | 2024-12-20T13:03:23Z |
| format | Article |
| id | doaj.art-0d342dfd7f124aa081d85f5b9a6bf33e |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
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| publishDate | 2009-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-0d342dfd7f124aa081d85f5b9a6bf33e2022-12-21T19:39:50ZengBMCMolecular Cancer1476-45982009-10-01818310.1186/1476-4598-8-83Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancerFernandez HervéBiola-Vidamment ArmellePallardy MarcEmilie DominiqueTouboul CyrilGaudin FrançoiseRedjimi NassimaPrévot SophieBalabanian KarlMachelon Véronique<p>Abstract</p> <p>Background</p> <p>Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation.</p> <p>Results</p> <p>GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, <it>P </it>< 0.00001, r = 0.56). They were also higher in tumor cells containing large amounts of phosphorylated protein kinase B (p-AKT) (unpaired t test, <it>P </it>< 0.0001). To assess the effect of GILZ on proliferation and AKT activation, we used the BG-1 cell line derived from ovarian tumor cells as a cellular model. GILZ expression was either enhanced by stable transfection or decreased by the use of small interfering (si) RNA targeting GILZ. We found that GILZ increased cell proliferation, phospho-AKT cellular content and AKT kinase activity. Further, GILZ upregulated cyclin D1 and phosphorylated retinoblastoma (p-Rb), downregulated cyclin-dependent kinase inhibitor p21, and promoted the entry into S phase of cell cycle.</p> <p>Conclusion</p> <p>The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.</p>http://www.molecular-cancer.com/content/8/1/83 |
| spellingShingle | Fernandez Hervé Biola-Vidamment Armelle Pallardy Marc Emilie Dominique Touboul Cyril Gaudin Françoise Redjimi Nassima Prévot Sophie Balabanian Karl Machelon Véronique Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer Molecular Cancer |
| title | Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer |
| title_full | Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer |
| title_fullStr | Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer |
| title_full_unstemmed | Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer |
| title_short | Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer |
| title_sort | identification of glucocorticoid induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer |
| url | http://www.molecular-cancer.com/content/8/1/83 |
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