التفاصيل البيبلوغرافية
| العنوان: |
Analysis of 14-3-3s expression in hyperproliferative skin diseases reveals selective loss associated with CpG-methylation in basal cell carcinoma. |
| المؤلفون: |
Lodygin, Dimitri1, Yazdi, Amir S2, Sander, Christian A2, Herzinger, Thomas2, Hermeking, Heiko1 |
| المصدر: |
Oncogene. 8/21/2003, Vol. 22 Issue 35, p5519-5524. 6p. 2 Color Photographs, 1 Diagram, 2 Charts. |
| مصطلحات موضوعية: |
*SKIN diseases, *BASAL cell carcinoma, *TUMOR suppressor proteins, *METHYLATION, *KERATINOCYTES, *CELL cycle |
| مستخلص: |
The p53-regulated 14-3-3s gene encodes an inhibitor of cell cycle progression essential for senescence and clonal evolution of keratinocytes in vitro. Here we analysed the in vivo expression of 14-3-3s protein in several skin diseases, which are characterized by hyperproliferative keratinocytes. Unexpectedly, the 14-3-3s protein was expressed at high levels in psoriasis (11 of 11 patients), condylomata acuminata (11/11), actinic keratoses (11/11) and squamous cell carcinomas (SCC) (11/11). However, keratinocytes that had undergone transformation to basal cell carcinoma (BCC) showed partial (10 of 41; 24.4%) or complete (19 of 41; 46.3%) loss of 14-3-3s protein expression. BCC (5/5), SCC (6/6) and actinic keratoses (7/7) concomitantly expressed the p53-homolog p63 and 14-3-3s at high levels, ruling out potential inhibitory effects of p63 isoforms on 14-3-3s transcription as the basis for loss of 14-3-3s expression. Of 41 BCC samples isolated by laser-capture microdissection, 28 (68.3%) showed CpG-hypermethylation of the 14-3-3s promoter combined with reduced or absent 14-3-3s protein levels in 22 cases (78.6%). Since it has been reported that BCC retain wild-type p16INK4A and here BCC with CpG-methylation of 14-3-3s did not show CpG-methylation of p16INK4A (0/17), silencing of 14-3-3s may contribute to evasion of senescence in BCC. As experimental removal of 14-3-3s sensitizes to DNA damage, silencing of 14-3-3s may explain the high efficacy of radiation therapy in the treatment of BCC.Oncogene (2003) 22, 5519-5524. doi:10.1038/sj.onc.1206854 [ABSTRACT FROM AUTHOR] |
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