Hematopoietic Progenitor Kinase 1, Mitogen-Activated Protein/Extracellular Signal-Related Protein Kinase Kinase Kinase 1, and phosphoMitogen-Activated Protein Kinase Kinase 4 are Overexpressed in Extramammary Paget Disease
| Autor: | Yue Qian, Satoshi Takeuchi, Masutaka Furue, Takeshi Nakahara, Ya Ting Tu, Masakazu Takahara, Lining Xie, Long Dugu, Yoichi Moroi, Gaku Tsuji |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male MAP Kinase Kinase 4 MAP Kinase Kinase Kinase 1 Dermatology Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase Pathology and Forensic Medicine MAP2K7 Biomarkers Tumor Humans Medicine ASK1 c-Raf Aged Neoplasm Staging MAP kinase kinase kinase biology business.industry Cyclin-dependent kinase 4 Cyclin-dependent kinase 2 General Medicine Middle Aged MAP Kinase Kinase Kinases Prognosis Immunohistochemistry Paget Disease Extramammary Cancer research biology.protein Female Cyclin-dependent kinase 9 business |
| Zdroj: | The American Journal of Dermatopathology. 33:681-686 |
| ISSN: | 0193-1091 |
| DOI: | 10.1097/dad.0b013e318215c3fb |
| Popis: | The c-Jun amino-terminal kinase (JNK) pathway seems to play important roles in the pathogenesis of several tumors, but its significance in extramammary Paget disease (EMPD) has not been investigated yet. The purpose of the study was to investigate the potential contribution of the JNK-associated molecules, such as hematopoietic progenitor kinase 1 (HPK1), mitogen-activated protein/extracellular signal-related protein kinase kinase kinase1 (MEKK1), transforming growth factor-β activated kinase 1 (TAK1), and phosphomitogen-activated protein kinase kinase 4 (p-MKK4) to the development of EMPD. Thirty-five paraffin-embedded EMPD specimens were subjected to immunohistochemical staining for HPK1, MEKK1, TAK1, and p-MKK4. All the 35 EMPD, including 13 dermal invasive EMPD and 2 lymph node metastasis, showed cytoplasmic overexpression of HPK1, MEKK1, and p-MKK4. The expression (%positive cells) of HPK1, MEKK1, and p-MKK4 in EMPD (92.3% ± 8.6%, 92.9% ± 8.6%, and 92.7% ± 7.4%, respectively) were significantly higher than in normal eccrine sweat gland cells (51.6% ± 10.4%, 44.7% ± 11.7%, 0% ± 0%). In addition, the expression of HPK1-, MEKK1-, and p-MKK4 in invasive EMPD was significantly higher than in noninvasive EMPD. Meanwhile, the expression of TAK1 was basically low and no significantly different between EMPD and normal controls. In conclusion, these results indicate that JNK pathway may play a role in the pathogenesis of EMPD. |
| Databáze: | OpenAIRE |
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