p27kip1 functional regulation in human cancer:: A potential target for therapeutic designs

被引:66
作者
Belletti, B
Nicoloso, MS
Schiappacassi, M
Chimienti, E
Berton, S
Lovat, F
Colombatti, A
Baldassarre, G
机构
[1] Ctr Riferimento Oncol, Ist Nazl Tumori, IRCCS, Div Oncol Sperimentale 2, I-33081 Aviano, Italy
[2] Ctr Riferimento Oncol, Ist Nazl Tumori, IRCCS, Mol Oncol Biomed Ctr, I-33081 Aviano, Italy
关键词
cell cycle regulation; CKI; p27; tumor progression; proteasome degradation; subcellular localization; gene therapy; adenoviral vectors;
D O I
10.2174/0929867054367149
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mitotic cell cycle is a tightly regulated process that ensures the correct division of one cell into two daughter cells. Progress along the different phases of the cell cycle is positively regulated by the sequential activation of a family of serine-threonine kinases called CDKs (Cyclin Dependent Kinases). Their activity. is counteracted by small proteins known as CDK inhibitors (CKI) that ensure the correct timing of CDK activation in the different phases of the cell cycle. The present review will deal with the role of one of this CKI, p27(kip1), in human cancer, focusing in particular on the mechanisms underlying its functional inactivation in tumor cells. p27(kip1) protein downregulation is usually achieved by proteasomal degradation and is often correlated to a worse prognosis in several types of human cancers, resulting in the reduction of disease free and overall survival. More recently, it has been proposed that p27(kip1) protein, rather than degraded, can be functionally inactivated. The mechanisms and the implications of these two types of p27(kip1) deregulation will be discussed and some potential therapeutic approaches targeting p27(kip1) functions will be proposed.
引用
收藏
页码:1589 / 1605
页数:17
相关论文
共 231 条
[31]  
Cordon-Cardo C, 1998, CANCER SURV, V32, P115
[32]   A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and lass of cyclin-Cdk activity in human breast cancer cells [J].
Craig, C ;
Wersto, R ;
Kim, M ;
Ohri, E ;
Li, ZW ;
Katayose, D ;
Lee, SJ ;
Trepel, J ;
Cowan, K ;
Seth, P .
ONCOGENE, 1997, 14 (19) :2283-2289
[33]  
Cusack JC, 2001, CANCER RES, V61, P3535
[34]   p27/kip I expression in normal epithelium, benign and neoplastic breast lesions [J].
De Paola, F ;
Vecci, AM ;
Granato, AM ;
Liverani, M ;
Monti, F ;
Innoceta, AM ;
Gianni, L ;
Saragoni, L ;
Ricci, M ;
Falcini, F ;
Amadori, D ;
Volpi, A .
JOURNAL OF PATHOLOGY, 2002, 196 (01) :26-31
[35]   Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse [J].
Di Cristofano, A ;
De Acetis, M ;
Koff, A ;
Cordon-Cardo, C ;
Pandolfi, PP .
NATURE GENETICS, 2001, 27 (02) :222-224
[36]   cdk-inhibitors-associated kinase activity: A possible determinant of malignant potential in smooth muscle tumors of the external soft tissue [J].
Dobashi, Y ;
Noguchi, T ;
Nasuno, S ;
Katayama, K ;
Kameya, T .
INTERNATIONAL JOURNAL OF CANCER, 2001, 94 (03) :353-362
[37]   Overexpression of Skp2 in carcinoma of the cervix does not correlate inversely with p27 expression [J].
Dowen, SE ;
Scott, A ;
Mukherjee, G ;
Stanley, MA .
INTERNATIONAL JOURNAL OF CANCER, 2003, 105 (03) :326-330
[38]   CDK INHIBITORS - ON THE THRESHOLD OF CHECKPOINTS AND DEVELOPMENT [J].
ELLEDGE, SJ ;
HARPER, JW .
CURRENT OPINION IN CELL BIOLOGY, 1994, 6 (06) :847-852
[39]   Malignant transformation of the esophageal mucosa is enhanced in p27 knockout mice [J].
Ellis, FH ;
Xu, XJ ;
Kulke, MH ;
LoCicero, J ;
Loda, M .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2001, 122 (04) :809-814
[40]  
Erlanson M, 1998, BLOOD, V92, P770