Gene expression of telomerase related proteins in human normal oral and ectocervical epithelial cells

被引:23
作者
Fujimoto, R
Kamata, N
Taki, M
Yokoyama, K
Tomonari, M
Nagayama, M
Yasumoto, S
机构
[1] Univ Tokushima, Dept Oral & Maxillofacial Surg 1, Sch Dent, Tokushima 7708504, Japan
[2] Kanagawa Canc Ctr, Res Inst, Mol Cell Biol Lab, Yokohama, Kanagawa, Japan
关键词
telomerase; hTERT; alternate splicing; telomeric repeat binding; factor (TRF); aging; normal oral keratinocytes; c-Myc; TRAP assay; RT-PCR;
D O I
10.1016/S1368-8375(03)00003-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We analyzed telomerase activities and gene expressions of telomerase components: hTERT, hTR, hTEP1, telomeric repeat binding factors: TRF1, TRF2, and c-myc, Max and Mad in human normal oral and ectocervical epithelial keratinocytes, comparing with those of squamous carcinoma cells and HPV16- or SV40-immortalized cells. Significant telomerase activity and hTERT expression were detected in primary keratinocytes. However, both were dramatically down-regulated during serial passages. The down-regulation of hTERT mRNA was associated with augmented expression of TRF1. Expression of c-myc was slightly decreased, whereas Mad was expressed in parallel with that of hTERT during passages. We also detected an alternate splicing of hTERT transcript in two of four cancer cells and normal aged epithelial cells. These results suggest that the senescence of normal oral and ectocervical keratinocytes is accompanied with up-regulation of TRF1 and down-regulation of telomerase activity due to transcriptional suppression of active form of hTERT in vitro. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:445 / 452
页数:8
相关论文
共 43 条
[1]  
APIWAT M, 1996, CANCER RES, V56, P3530
[2]   MAD - A HETERODIMERIC PARTNER FOR MAX THAT ANTAGONIZES MYC TRANSCRIPTIONAL ACTIVITY [J].
AYER, DE ;
KRETZNER, L ;
EISENMAN, RN .
CELL, 1993, 72 (02) :211-222
[3]   TRF1 is a dimer and bends telomeric DNA [J].
Bianchi, A ;
Smith, S ;
Chong, L ;
Elias, P ;
deLange, T .
EMBO JOURNAL, 1997, 16 (07) :1785-1794
[4]   Telomeric localization of TRF2, a novel human telobox protein [J].
Bilaud, T ;
Brun, C ;
Ancelin, K ;
Koering, CE ;
Laroche, T ;
Gilson, E .
NATURE GENETICS, 1997, 17 (02) :236-239
[5]   Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2 [J].
Broccoli, D ;
Smogorzewska, A ;
Chong, L ;
deLange, T .
NATURE GENETICS, 1997, 17 (02) :231-235
[6]   A HUMAN TELOMERIC PROTEIN [J].
CHONG, L ;
VANSTEENSEL, B ;
BROCCOLI, D ;
ERDJUMENTBROMAGE, H ;
HANISH, J ;
TEMPST, P ;
DELANGE, T .
SCIENCE, 1995, 270 (5242) :1663-1667
[7]   The hTERTα splice variant is a dominant negative inhibitor of telomerase activity [J].
Colgin, LM ;
Wilkinson, C ;
Englezou, A ;
Kilian, A ;
Robinson, MO ;
Reddel, RR .
NEOPLASIA, 2000, 2 (05) :426-432
[8]   TELOMERASE ACTIVITY IN NORMAL LEUKOCYTES AND IN HEMATOLOGIC MALIGNANCIES [J].
COUNTER, CM ;
GUPTA, J ;
HARLEY, CB ;
LEBER, B ;
BACCHETTI, S .
BLOOD, 1995, 85 (09) :2315-2320
[9]   TELOMERASE ACTIVITY IN HUMAN OVARIAN-CARCINOMA [J].
COUNTER, CM ;
HIRTE, HW ;
BACCHETTI, S ;
HARLEY, CB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) :2900-2904
[10]   Expression of telomerase components in oral keratinocytes and squamous cell carcinomas [J].
Fujimoto, R ;
Kamata, N ;
Yokoyama, K ;
Ueda, N ;
Satomura, K ;
Hayashi, E ;
Nagayama, M .
ORAL ONCOLOGY, 2001, 37 (02) :132-140