Cytokeratin 8 silencing in human nasopharyngeal carcinoma cells leads to cisplatin sensitization.
By comparing protein profiles of nasopharyngeal carcinoma HONE1 cells to transformed nasopharyngeal epithelial NP 69 cells, several clusters of differentially expressed proteins were identified. The increased expression of cytokeratin 8 (CK8) and pyruvate kinase M2 was a common feature in four NPC cell lines compared to the two transformed epithelial cell lines. Suppression of CK8 was associated with the sensitivity to cisplatin in HONE1 cells; while overexpression of CK8 provided resistance to cisplatin-mediated apoptosis; and this protection occurred through an enhanced phosphorylation of c-Jun NH(2)-terminal kinase (JNK). Our findings implicate an underlying molecular mechanism in which CK8 is required for cisplatin resistance.
Wang
Ying
Y
Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China.
He
Qing-Yu
QY
Tsao
Sai-Wah
SW
Cheung
Yim-Hing
YH
Wong
Anita
A
Chiu
Jen-Fu
JF
D017209:Apoptosis; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053533:Keratin-8 / Q000502:physiology*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D040081:Protein Array Analysis; D014162:Transfection
D053533:Keratin-8; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin