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Enhanced activity of cyclin A-associated kinase in immortalized human fibroblasts

✍ Scribed by Ryuichiro Ohashi; Masahiro Miyazaki; Kazuo Fushimi; Toshiya Tsuji; Yusuke Inoue; Nobuyoshi Shimizu; Masayoshi Namba


Publisher
John Wiley and Sons
Year
1999
Tongue
French
Weight
164 KB
Volume
82
Category
Article
ISSN
0020-7136

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✦ Synopsis


Deregulation of cell cycle regulatory mechanisms leads to disruption of normal control of cell growth and may be associated with neoplastic transformation. To determine whether immortalized human cells have alterations in their cell cycle regulatory mechanisms, we analyzed cell cycle regulatory proteins in 2 immortalized human fibroblast cell lines, KMST-6 and OUMS-24/P6X, established by repeated irradiation with 60 Co gamma rays alone or mutant p53 gene transfection plus X-ray irradiation, respectively. Both the immortalized cell lines had markedly enhanced activity of cyclin A-associated kinase as compared with their normal counterparts. The high activity of cyclin A-associated kinase was well correlated with the increased expression of cyclin A mRNA and its protein. In addition, the immortalized cell lines showed significantly reduced amounts of p21 Cip1/Waf1/Sdi1 , a potent inhibitor of cyclin dependent kinases. Furthermore, among the pRb family of proteins, p107 and p130, were hyperphosphorylated in both the immortalized cell lines, suggesting possible participation in upregulation of cyclin A associated kinase activity. These changes represent some important characteristics of immortalized cells. Int.


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