HPV related VIN: Highly proliferative and diminished responsiveness to extracellular signals
| Autor: | Wilfred F. J. van IJcken, Lindy A.M. Santegoets, Manon van Seters, Patricia C. Ewing, Leen J. Blok, Theo J.M. Helmerhorst, Payman Hanifi-Moghaddam, Claudia Heijmans-Antonissen, Willem I. van der Meijden, Peter J. van der Spek |
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| Přispěvatelé: | Obstetrics & Gynecology, Anesthesiology, Medical Oncology, Pathology, Cell biology, Dermatology |
| Rok vydání: | 2007 |
| Předmět: |
Adult
Cancer Research Microarray Angiogenesis Cell Cycle Proteins Biology Alphapapillomavirus Paracrine signalling Gene expression medicine Humans Cyclin Cell Proliferation Vulvar Neoplasms Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Reproducibility of Results Middle Aged Vulvar intraepithelial neoplasia medicine.disease Oncology Significance analysis of microarrays Immunology Cancer research Female Signal transduction Precancerous Conditions Carcinoma in Situ Signal Transduction |
| Zdroj: | International Journal of Cancer, 121(4), 759-766. Wiley-Liss Inc. |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.22769 |
| Popis: | Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell-cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observed that these processes have not become significantly disregulated in VIN. In conclusion: although VIN is still a premalignant disease, it already displays several hallmarks of cancer. |
| Databáze: | OpenAIRE |
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