Reprogramming of replicative senescence in hepatocellular carcinoma-derived cells

被引：51

作者：

Ozturk, N

Erdal, E

Mumcuoglu, M

Akcali, KC

Yalcin, O

Senturk, S

Arslan-Ergul, A

Gur, B

Yulug, I

Cetin-Atalay, R

Yakicier, C

Yagci, T

Tez, M

Ozturk, M ^{[1
]}

机构：

[1] Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey

[2] Ankara Numune Training & Res Hosp, Dept Surg 5, TR-06100 Ankara, Turkey

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2006年 / 103卷 / 07期

关键词：

immortality; liver cancer; SIP1; telomerase; p53;

D O I：

10.1073/pnas.0510877103

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tumor cells have the capacity to proliferate indefinitely that is qualified as replicative immortality. This ability contrasts with the intrinsic control of the number of cell divisions in human somatic tissues by a mechanism called replicative senescence. Replicative immortality is acquired by inactivation of p53 and p16(INK4a) genes and reactivation of hTERT gene expression. It is unknown whether the cancer cell replicative immortality is reversible. Here, we show the spontaneous induction of replicative senescence in p53-and p16(INK4a)-deficient hepatocellular carcinoma cells. This phenomenon is characterized with hTERT repression, telomere shortening, senescence arrest, and tumor suppression. SIP1 gene (ZFHX1B) is partly responsible for replicative senescence, because short hairpin RNA-mediated SIP1 inactivation released hTERT repression and rescued clonal hepatocellular carcinoma cells from senescence arrest.

引用

页码：2178 / 2183

页数：6

共 35 条

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