Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer
| Autor: | Gareth I. Owen, Gabriella A. Di Capua, Rebecca Graumann, Paola Casanello, Jorge Brañes, Marcos Vasquez, Alejandro H. Corvalan, Juan E. Oyarzún, Uwe Zangemeister-Wittke, Annemarie Ziegler, Christine Liao, Iris Delgado, Iván Roa |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology lcsh:Medicine Gene Expression Artificial Gene Amplification and Extension Polymerase Chain Reaction Biochemistry Ovarian tumor Gene expression Medicine and Health Sciences Small interfering RNAs RNA Small Interfering lcsh:Science 610 Medicine & health Ovarian Neoplasms Regulation of gene expression DNA methylation Multidisciplinary Cell Differentiation Phenotype Chromatin Ovarian Cancer Gene Expression Regulation Neoplastic Survival Rate Nucleic acids Oncology Female Epigenetics DNA modification Chromatin modification Research Article Chromosome biology Cell biology medicine.medical_specialty Down-Regulation Nerve Tissue Proteins Biology Real-Time Polymerase Chain Reaction Research and Analysis Methods 03 medical and health sciences Malignant Tumors Cell Line Tumor Genetics medicine Humans Gene silencing Gene Silencing Molecular Biology Techniques Non-coding RNA Molecular Biology Differentiated Tumors lcsh:R Biology and Life Sciences Cancers and Neoplasms DNA Reverse Transcriptase-Polymerase Chain Reaction medicine.disease Gene regulation 030104 developmental biology Cancer cell Cancer research RNA lcsh:Q CpG Islands Ovarian cancer Gynecological Tumors |
| Zdroj: | Graumann, Rebecca; Di Capua, Gabriella A; Oyarzún, Juan E; Vásquez, Marcos A; Liao, Christine; Brañes, Jorge A; Roa, Iván; Casanello, Paola; Corvalán, Alejandro H; Owen, Gareth I; Delgado, Iris; Zangemeister-Wittke, Uwe; Ziegler, Annemarie (2017). Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer. PLoS ONE, 12(5), e0177244. Public Library of Science 10.1371/journal.pone.0177244 PLoS ONE PLoS ONE, Vol 12, Iss 5, p e0177244 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0177244 |
| Popis: | Teneurins are a family of highly conserved pair-rule proteins involved in morphogenesis and development of the central nervous system. Their function in adult tissues and in disease is largely unknown. Recent evidence suggests a role for dysregulated expression of Teneurins in human tumors, but systematic investigations are missing. Here, we investigated Teneurin-2 and Teneurin-4 expression in various cancer cell lines and in ovarian tumor tissues. Teneurin-2 and Teneurin-4 were expressed in most of the breast cancer cell lines tested. Teneurin-4 was also detected in ovarian cancer cell lines, and throughout ovarian tumors and normal ovary tissue. Ovarian tumors with low Teneurin-4 expression showed less differentiated phenotypes and these patients had shorter mean overall survival. Similarly, Teneurin-2 expression correlated with overall survival as well, especially in patients with serous tumors. In the various cell lines, 5-Aza-cytidine-induced changes in DNA methylation did not alter expression of Teneurin-2 and Teneurin-4, despite the existence of predicted CpG islands in both genes. Interestingly, however, we found evidence for the control of Teneurin-2 expression by the oncogenic growth factor FGF8. Furthermore, we identified multiple transcript splicing variants for Teneurin-2 and Teneurin-4, indicating complex gene expression patterns in malignant cells. Finally, downregulation of Teneurin-4 expression using siRNA caused a cell-type dependent increase in proliferation and resistance to cisplatin. Altogether, our data suggest that low Teneurin-4 expression provides a growth advantage to cancer cells and marks an undifferentiated state characterized by increased drug resistance and clinical aggressiveness. We conclude that Teneurin-2 and Teneurin-4 expression levels could be of prognostic value in ovarian cancer. |
| Databáze: | OpenAIRE |
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