HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 5, 2776-2784, February 2, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/5/2776    most recent M607234200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lin, H. Articles by Lin, S.-Y. Search for Related Content PubMed PubMed Citation Articles by Lin, H. Articles by Lin, S.-Y. Social Bookmarking                      What's this?

Cdk5 Regulates STAT3 Activation and Cell Proliferation in Medullary Thyroid Carcinoma Cells^*

Ho Lin¹, Mei-Chih Chen, Chih-Yuan Chiu, Yuh-Min Song^¶, and Shih-Yi Lin^||

From the Department of Life Science, National Chung Hsing University, Taichung 40227, ^¶Section of Biochemistry, Department of Medical Laboratories, ^||Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung 40705, and the Department of Physiology, National Yang Ming University, Taipei 11221, Taiwan

The biological behaviors of thyroid cancer are varied, and the pathological mechanisms remain unclear. Some reports indicated an apparent aggregation of amyloid accompanying medullary thyroid carcinoma (MTC). Amyloid aggregation in neurodegeneration leads to hyperactivation of Cdk5 and subsequent neuronal death. Based on the connection with amyloid, the role of Cdk5 in MTC is worthy of investigation. Initially, the expression of Cdk5 and its activator, p35, in MTC cell lines was identified. Cdk5 inhibition by specific inhibitors or short interfering RNA decreased the proliferation of MTC cell lines, which reveals the importance of Cdk5 in MTC cell growth. Although p35 cleavage has been considered as an important element in neurodegeneration, it seems that p35 cleavage was not a major cause in Cdk5 activity-dependent MTC cell proliferation because neither Cdk5 activity nor cell growth was affected by the inhibition of p35 cleavage. Clearance of amyloid by antibody neutralization indicated that MTC cell proliferation was supported by calcitonin-derived extracellular amyloid and subsequent Her2 and Cdk5 activation. Significantly, the STAT3 pathway was involved in Cdk5-dependent proliferation of MTC cells through Ser-727 phosphorylation. In addition, Cdk5 inhibition reduced nuclear distributions of both the Cdk5-p35 complex and phospho-STAT3 in MTC cells. Finally, Cdk5 inhibition retarded tumor formation in vivo accompanying the reduction of phospho-STAT3. Our findings suggest the first demonstration of a novel and specific role for Cdk5 kinase in supporting the proliferation of the medullary thyroid carcinoma cells and could shed light on a new field for diagnosis and therapy of thyroid cancer.

Received for publication, July 31, 2006 , and in revised form, December 1, 2006.

^* This work was supported by Taichung Veterans General Hospital and National Chung Hsing University Grant TCVGH-NCHU-957612 (to H. L.), Taichung, Taiwan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S4.

¹ To whom correspondence should be addressed: Dept. of Life Science, National Chung Hsing University, 250, Kuo Kuang Rd., Taichung 40227, Taiwan. Tel.: 886-4-22840416 (ext. 617); Fax: 886-4-22874740; E-mail: hlin{at}dragon.nchu.edu.tw.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Lin, M.-C. Chen, and C.-T. Ku Cyclin-Dependent Kinase 5 Regulates Steroidogenic Acute Regulatory Protein and Androgen Production in Mouse Leydig Cells Endocrinology, January 1, 2009; 150(1): 396 - 403. [Abstract] [Full Text] [PDF]

				K.-H. Sun, Y. de Pablo, F. Vincent, E. O. Johnson, A. K. Chavers, and K. Shah Novel Genetic Tools Reveal Cdk5's Major Role in Golgi Fragmentation in Alzheimer's Disease Mol. Biol. Cell, July 1, 2008; 19(7): 3052 - 3069. [Abstract] [Full Text] [PDF]

				R. Liu, B. Tian, M. Gearing, S. Hunter, K. Ye, and Z. Mao Cdk5-mediated regulation of the PIKE-A-Akt pathway and glioblastoma cell invasion PNAS, May 27, 2008; 105(21): 7570 - 7575. [Abstract] [Full Text] [PDF]