Article (Scientific journals)
Cervix carcinoma is associated with an up-regulation and nuclear localization of the dual-specificity protein phosphatase VHR.
Henkens, Rachel; Delvenne, Philippe; Arafa, Mohammad et al.
2008In BMC Cancer, 8, p. 147
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Keywords :
cervix carcinoma; VHR phosphatase
Abstract :
[en] BACKGROUND: The 21-kDa Vaccinia virus VH1-related (VHR) dual-specific protein phosphatase (encoded by the DUSP3 gene) plays a critical role in cell cycle progression and is itself regulated during the cell cycle. We have previously demonstrated using RNA interference that cells lacking VHR arrest in the G1 and G2 phases of the cell cycle and show signs of beginning of cell senescence. METHODS: In this report, we evaluated successfully the expression levels of VHR protein in 62 hysterectomy or conization specimens showing the various (pre) neoplastic cervical epithelial lesions and 35 additional cases of hysterectomy performed for non-cervical pathologies, from patients under 50 years of age. We used a tissue microarray and IHC technique to evaluate the expression of the VHR phosphatase. Immunofluorescence staining under confocal microscopy, Western blotting and RT-PCR methods were used to investigate the localization and expression levels of VHR. RESULTS: We report that VHR is upregulated in (pre) neoplastic lesions (squamous intraepithelial lesions; SILs) of the uterine cervix mainly in high grade SIL (H-SIL) compared to normal exocervix. In the invasive cancer, VHR is also highly expressed with nuclear localization in the majority of cells compared to normal tissue where VHR is always in the cytoplasm. We also report that this phosphatase is highly expressed in several cervix cancer cell lines such as HeLa, SiHa, CaSki, C33 and HT3 compared to primary keratinocytes. The immunofluorescence technique under confocal microscopy shows that VHR has a cytoplasmic localization in primary keratinocytes, while it localizes in both cytoplasm and nucleus of the cancer cell lines investigated. We report that the up-regulation of this phosphatase is mainly due to its post-translational stabilization in the cancer cell lines compared to primary keratinocytes rather than increases in the transcription of DUSP3 locus. CONCLUSION: These results together suggest that VHR can be considered as a new marker for cancer progression in cervix carcinoma and potential new target for anticancer therapy.
Research center :
GIGA‐R - Giga‐Research - ULiège
Disciplines :
Oncology
Author, co-author :
Henkens, Rachel ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Arafa, Mohammad
Moutschen, Michel  ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Zeddou, Mustapha ;  Université de Liège - ULiège > Département des sciences cliniques > Hématologie
Tautz, Lutz
Boniver, Jacques ;  Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Mustelin, Tomas
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Language :
English
Title :
Cervix carcinoma is associated with an up-regulation and nuclear localization of the dual-specificity protein phosphatase VHR.
Publication date :
2008
Journal title :
BMC Cancer
eISSN :
1471-2407
Publisher :
BioMed Central, United Kingdom
Volume :
8
Pages :
147
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 08 January 2009

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