|
|
Blood, 1 February 2008, Vol. 111, No. 3, pp. 1644-1653.
Prepublished online as a Blood First Edition Paper on November 19, 2007; DOI 10.1182/blood-2007-05-088591.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Protein kinase C–associated kinase is required for NF- B signaling and survival in diffuse large B-cell lymphoma cells
Sang-Woo Kim1,
David W. Oleksyn2,3,
Randall M. Rossi4,
Craig T. Jordan2,4,
Ignacio Sanz3,
Luojing Chen2,3, and
Jiyong Zhao1
1 Department of Biomedical Genetics, University of Rochester Medical Center, NY;
2 Center for Pediatric Biomedical Research, University of Rochester Medical Center, NY;
3 Division of Allergy/Immunology and Rheumatology, University of Rochester Medical Center, NY; and
4 James P. Wilmot Cancer Center, University of Rochester Medical Center, NY
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma. Despite recent advances in treatment, less than 50% of the patients are cured with current multiagent chemotherapy. Abnormal NF- B activity not only contributes to tumor development but also renders cancer cells resistant to chemotherapeutic agents. Identifying and targeting signaling molecules that control NF-B activation in cancer cells may thus yield more effective therapy for DLBCL. Here, we show that while overexpression of protein kinase C–associated kinase (PKK) activates NF-B signaling in DLBCL cells, suppression of PKK expression inhibits NF-B activity in these cells. In addition, we show that NF-B activation induced by B cell–activating factor of tumor necrosis factor family (BAFF) in DLBCL cells requires PKK. Importantly, we show that knockdown of PKK impairs the survival of DLBCL cells in vitro and inhibits tumor growth of xenografted DLBCL cells in mice. Suppression of PKK expression also sensitizes DLBCL cells to treatment with chemotherapeutic agents. Together, these results indicate that PKK plays a pivotal role in the survival of human DLBCL cells and represents a potential target for DLBCL therapy.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
| |
