Expression of minichromosome maintenance 2 (MCM2), Ki-67, and cell-cycle-related molecules, and apoptosis in the normal-dysplasia-carcinoma sequence of the oral mucosa

被引:44
作者
Kodani, I
Shomori, K
Osaki, M
Kuratate, I
Ryoke, K
Ito, H
机构
[1] Tottori Univ, Fac Med, Dept Pathol 1, Yonago, Tottori 6838503, Japan
[2] Tottori Univ, Fac Med, Dept Oral & Maxillofacial Surg, Yonago, Tottori 6838503, Japan
关键词
oral dysplasia; squamous cell carcinoma; minichromosome maintenance 2; Ki-67; P53; P21; P27; apoptosis;
D O I
10.1159/000048770
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective: We examined cell cycle and cell death bio-marker trends with the normal-dysplasia-carcinoma sequence of the: oral epithelia analyzing the pathological significance of a. new biomarker, minichromosome maintenance 2 (MCM2). Methods: This study analyzed 12 Patients with normal oral epithelia, 69, with dysplasia, and 35 with squamous cell carcinoma (SCC); in 13 patients, SCCs were preceded by dysplasia. The sections were immunostained for MCM2, Ki-67, P53, P27(Kip1) and P21(CIP1/WAF1), and conducted by TUNEL methods. Western blot analysis of MCM2 was performed in the 4 human cultured oral SCCs, all of which showed the expression. Results: Significantly higher labeling indices (LI; %) of MCM2, Ki-67, and P53, as well as lower LI of TUNEL indices (TI; %), P27, and P21 were noted in the SCCs than in the dysplasias. The 13 dysplasias developed SCC with significantly higher LI of MCM2 and P53, and lower LI of P21 than the other dysplasias (each p, < 0.05). The LI of MCM2, P21 and the TI were not correlated with P53 expression. Conclusions: Oral dysplasia was characterized by lower cell proliferation and a higher frequency of cell death compared to SCCs. The higher LI of MCM2 and P53 and the lower LI of P21 might predict malignant transformation of oral dysplasia. MCM2 is regulated via a P53-independent pathway, and: a useful biomarker of proliferating cells. Copyright (C) 2002 S.Karger AG, Basel.
引用
收藏
页码:150 / 158
页数:9
相关论文
共 50 条
[21]   DIFFERENTIAL INDUCTION OF TRANSCRIPTIONALLY ACTIVE P53 FOLLOWING UV OR IONIZING-RADIATION - DEFECTS IN CHROMOSOME INSTABILITY SYNDROMES [J].
LU, X ;
LANE, DP .
CELL, 1993, 75 (04) :765-778
[22]   ORAL EPITHELIAL DYSPLASIA AND THE DEVELOPMENT OF INVASIVE SQUAMOUS-CELL CARCINOMA [J].
LUMERMAN, H ;
FREEDMAN, P ;
KERPEL, S .
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS, 1995, 79 (03) :321-329
[23]   MCM3 COMPLEX REQUIRED FOR CELL-CYCLE REGULATION OF DNA-REPLICATION IN VERTEBRATE CELLS [J].
MADINE, MA ;
KHOO, CY ;
MILLS, AD ;
LASKEY, RA .
NATURE, 1995, 375 (6530) :421-424
[24]  
MATHEVET P, 2000, GYNECOL OBSTET FERTI, V1, P44
[25]   Alterations of p16/CDKN2, p53 and ras genes in oral squamous cell carcinomas and premalignant lesions [J].
Matsuda, H ;
Konishi, N ;
Hiasa, Y ;
Hayashi, I ;
Tsuzuki, T ;
Tao, M ;
Kitahori, Y ;
Yoshioka, N ;
Kirita, T ;
Sugimura, M .
JOURNAL OF ORAL PATHOLOGY & MEDICINE, 1996, 25 (05) :232-238
[26]  
MIYASHITA T, 1995, CELL, V80, P293
[27]   THE MDM-2 ONCOGENE PRODUCT FORMS A COMPLEX WITH THE P53 PROTEIN AND INHIBITS P53-MEDIATED TRANSACTIVATION [J].
MOMAND, J ;
ZAMBETTI, GP ;
OLSON, DC ;
GEORGE, D ;
LEVINE, AJ .
CELL, 1992, 69 (07) :1237-1245
[28]   VARIANT SUBLINES WITH DIFFERENT METASTATIC POTENTIALS SELECTED IN NUDE-MICE FROM HUMAN ORAL SQUAMOUS-CELL CARCINOMAS [J].
MOMOSE, F ;
ARAIDA, T ;
NEGISHI, A ;
ICHIJO, H ;
SHIODA, S ;
SASAKI, S .
JOURNAL OF ORAL PATHOLOGY & MEDICINE, 1989, 18 (07) :391-395
[29]  
Munirajan AK, 1998, INT J ONCOL, V13, P971
[30]   MUTATIONS IN THE P53 GENE OCCUR IN DIVERSE HUMAN-TUMOR TYPES [J].
NIGRO, JM ;
BAKER, SJ ;
PREISINGER, AC ;
JESSUP, JM ;
HOSTETTER, R ;
CLEARY, K ;
BIGNER, SH ;
DAVIDSON, N ;
BAYLIN, S ;
DEVILEE, P ;
GLOVER, T ;
COLLINS, FS ;
WESTON, A ;
MODALI, R ;
HARRIS, CC ;
VOGELSTEIN, B .
NATURE, 1989, 342 (6250) :705-708