Developmentally imprinted genes as markers for bladder tumor progression

被引:51
作者
Cooper, MJ
Fischer, M
Komitowski, D
Shevelev, A
Schulze, E
Ariel, I
Tykocinski, ML
Miron, S
Ilan, J
DeGroot, N
Hochberg, A
机构
[1] CASE WESTERN RESERVE UNIV,SCH MED,DEPT MED,CLEVELAND,OH 44106
[2] CASE WESTERN RESERVE UNIV,SCH MED,DEPT PATHOL,CLEVELAND,OH 44106
[3] GERMAN CANC RES CTR,W-6900 HEIDELBERG,GERMANY
[4] HADASSAH UNIV HOSP,DEPT PATHOL,MT SCOPUS,ISRAEL
[5] HEBREW UNIV JERUSALEM,SILBERMAN INST LIFE SCI,DEPT BIOL CHEM,JERUSALEM,ISRAEL
关键词
bladder neoplasms; insulin-like growth factor II; tumor markers; biological; genomic imprinting;
D O I
10.1016/S0022-5347(01)66120-2
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Developmentally imprinted genes, such as H19 and insulin-like growth factor-II (IGF-II), play an important role during human embryogenesis and also have been implicated in the pathogenesis of embryonal tumors of childhood. Since H19 is expressed in human fetal bladder, we evaluated 35 bladder carcinomas for H19 expression by in situ hybridization analysis and correlated expression with tumor grade. As a prelude to gene transfer studies to determine if H19 is a bladder tumor oncogene, we also evaluated bladder cell lines for expression of H19, IGF-II, IGF-I and the type I IGF receptor. Materials and Methods: H19 expression was evaluated by in situ hybridization analysis in bladder tumor specimens. Northern analysis was used to evaluate the expression of H19, IGF-II, IGF-I and the type I IGF receptor in bladder cell lines. Results: H19 was expressed preferentially in advanced stage tumors: 2 of 12 grade I tumors were H19 positive, whereas 9 of 11 grade II and 7 of 10 grade III tumors expressed H19 (p = 0.004). Additionally, 6 of 6 carcinoma in situ tumors were H19 positive, whereas normal bladder mucosa cells were H19 negative. We found that 3 of 11 cell lines (HT-1376, HT-1197 and 5637) express high levels of H19 mRNA, and each of these cell lines and J82 also express IGF-II. All cell lines examined expressed the type I IGF receptor, whereas there was no detectable IGF-I mRNA. Conclusions: These data demonstrate that H19 is an oncodevelopmental marker of bladder tumor progression and raise the possibility that H19 may have oncogenic properties in bladder cancer.
引用
收藏
页码:2120 / 2127
页数:8
相关论文
共 64 条
  • [1] THE IMPRINTED H19 GENE AS A TUMOR-MARKER IN BLADDER-CARCINOMA
    ARIEL, I
    LUSTIG, O
    SCHNEIDER, T
    PIZOV, G
    SAPPIR, M
    DEGROOT, N
    HOCHBERG, A
    [J]. UROLOGY, 1995, 45 (02) : 335 - 338
  • [2] BABU VR, 1987, CANCER RES, V47, P6800
  • [3] PARENTAL IMPRINTING OF THE MOUSE H19 GENE
    BARTOLOMEI, MS
    ZEMEL, S
    TILGHMAN, SM
    [J]. NATURE, 1991, 351 (6322) : 153 - 155
  • [4] EPIGENETIC MECHANISMS UNDERLYING THE IMPRINTING OF THE MOUSE H19-GENE
    BARTOLOMEI, MS
    WEBBER, AL
    BRUNKOW, ME
    TILGHMAN, SM
    [J]. GENES & DEVELOPMENT, 1993, 7 (09) : 1663 - 1673
  • [5] HUMAN IMPRINTED GENES AS ONCODEVELOPMENTAL MARKERS
    BIRAN, H
    ARIEL, I
    DEGROOT, N
    SHANI, A
    HOCHBERG, A
    [J]. TUMOR BIOLOGY, 1994, 15 (03) : 123 - 134
  • [6] THE PRODUCT OF THE H19 GENE MAY FUNCTION AS AN RNA
    BRANNAN, CI
    DEES, EC
    INGRAM, RS
    TILGHMAN, SM
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (01) : 28 - 36
  • [7] CELLULAR AND HUMORAL IMMUNE RESPONSES TO HUMAN URINARY BLADDER CARCINOMAS
    BUBENIK, J
    PERLMANN, P
    HELMSTEIN, K
    MOBERGER, G
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1970, 5 (03) : 310 - +
  • [8] FREQUENCY OF H-RAS MUTATIONS IN HUMAN BLADDER-CANCER DETECTED BY DIRECT SEQUENCING
    BURCHILL, SA
    NEAL, DE
    LUNEC, J
    [J]. BRITISH JOURNAL OF UROLOGY, 1994, 73 (05): : 516 - 521
  • [9] CHIRGWIN JM, 1979, BIOCHEMISTRY-US, V18, P5297
  • [10] INSULIN-LIKE GROWTH FACTOR-II BINDING AND ACTION IN HUMAN-FETAL FIBROBLASTS
    CONOVER, CA
    ROSENFELD, RG
    HINTZ, RL
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 1987, 133 (03) : 560 - 566