Suppression of ING1 expression in sporadic breast cancer

被引:125
作者
Toyama, T
Iwase, H
Watson, P
Muzik, H
Saettler, E
Magliocco, A
DiFrancesco, L
Forsyth, P
Garkavtsev, I
Kobayashi, S
Riabowol, K
机构
[1] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada
[2] Univ Calgary, Fac Med, Dept Oncol, Calgary, AB T2N 4N1, Canada
[3] Univ Calgary, Fac Med, So Alberta Canc Res Ctr, Calgary, AB T2N 4N1, Canada
[4] Univ Calgary, Fac Med, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada
[5] Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[6] Univ Manitoba, Fac Med, Dept Pathol, Winnipeg, MB R3E 0W3, Canada
[7] Univ Saskatchewan, Royal Hosp, Coll Med, Dept Pathol, Saskatoon, SK S7N 0W8, Canada
[8] Foothills Prov Gen Hosp, Dept Pathol, Calgary, AB T2N 2T9, Canada
关键词
ING1; tumour suppressor gene; breast cancer; SSCP; mutation; expression;
D O I
10.1038/sj.onc.1202905
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Down regulation of the ING1 candidate tumour suppressor promotes growth in soft agar and focus formation in vitro and tumour formation in vivo. ING1 encodes a nuclear, cell cycle-regulated protein, overexpression of which efficiently blocks cell growth and is capable of inducing apoptosis in different experimental systems. Here we present the first report of ING1 mutation and expression analysis in a total of 452 cancer samples. One germline missense alteration and three germline silent alterations were detected in 377 primary breast cancers while marked (2-10-fold) decreases in ING1 mRNA expression were seen in 44% of primary breast cancers and in ten of ten breast cancer cell lines examined. Furthermore, the majority of breast cancers (58%) showing decreased ING1 expression had metastasized to regional lymph nodes whereas only 9% of cancers with elevated ING1 expression, compared to adjacent normal tissues, were metastatic. Thus, ING1 mutation is very rare in breast or ovarian cancers, however, repression of ING1 expression frequently accompanies tumour development of breast cancer.
引用
收藏
页码:5187 / 5193
页数:7
相关论文
共 28 条
[1]  
Brenner AJ, 1996, CLIN CANCER RES, V2, P1993
[2]   RECENT DEVELOPMENTS IN THE MOLECULAR-GENETIC UNDERSTANDING OF BREAST-CANCER [J].
DEVILEE, P ;
SCHUURING, E ;
VANDEVIJVER, MJ ;
CORNELISSE, CJ .
CRITICAL REVIEWS IN ONCOGENESIS, 1994, 5 (2-3) :247-270
[3]   Suppression subtractive hybridization: A method for generating differentially regulated or tissue-specific cDNA probes and libraries [J].
Diatchenko, L ;
Lau, YFC ;
Campbell, AP ;
Chenchik, A ;
Moqadam, F ;
Huang, B ;
Lukyanov, S ;
Lukyanov, K ;
Gurskaya, N ;
Sverdlov, ED ;
Siebert, PD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :6025-6030
[4]  
Dobrovic A, 1997, CANCER RES, V57, P3347
[5]   Specific monoclonal antibody raised against the p33ING1 tumor suppressor [J].
Garkavtsev, I ;
Boland, D ;
Mai, J ;
Wilson, H ;
Veillette, C ;
Riabowol, K .
HYBRIDOMA, 1997, 16 (06) :537-540
[6]   Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33(ING1) candidate tumor suppressor [J].
Garkavtsev, I ;
Riabowol, K .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (04) :2014-2019
[7]   Cellular localization and chromosome mapping of a novel candidate tumor suppressor gene (ING1) [J].
Garkavtsev, I ;
Demetrick, D ;
Riabowol, K .
CYTOGENETICS AND CELL GENETICS, 1997, 76 (3-4) :176-178
[8]   Suppression of the novel growth inhibitor p33(ING1) promotes neoplastic transformation [J].
Garkavtsev, I ;
Kazarov, A ;
Gudkov, A ;
Riabowol, K .
NATURE GENETICS, 1996, 14 (04) :415-420
[9]   The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control [J].
Garkavtsev, I ;
Grigorian, IA ;
Ossovskaya, VS ;
Chernov, MV ;
Chumakov, PM ;
Gudkov, AV .
NATURE, 1998, 391 (6664) :295-298
[10]  
HARVEY MB, 1995, DEVELOPMENT, V121, P1005