Development of spontaneous tumours and intestinal lesions in Fhit gene knockout mice

被引：22

作者：

Fujishita, T

Doi, Y

Sonoshita, M

Hiai, H

Oshima, M

Huebner, K

Croce, CM

Taketo, MM

机构：

[1] Kyoto Univ, Dept Pharmacol, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan

[2] Univ Tokyo, Lab Biocmed Genet, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan

[3] Kyoto Univ, Dept Pathol & Biol Dis, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan

[4] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Inst, Philadelphia, PA 19107 USA

来源：

BRITISH JOURNAL OF CANCER | 2004年 / 91卷 / 08期

关键词：

fragile histidine triad gene (FHIT); tumour suppressor gene; intestinal polyps; intestinal lesions; Apc; beta-catenin;

D O I：

10.1038/sj.bjc.6602182

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The fragile histidine triad (FHIT) gene is frequently inactivated in various types of tumours. However, the system-wide pathology caused by FHIT inactivation has not been examined in detail. Here we demonstrate that Fhit gene knockout mice develop tumours in the lymphoid tissue, liver, uterus, testis, forestomach and small intestine, together with structural abnormalities in the small intestinal mucosa. These results suggest that Fhit plays important roles in systemic tumour suppression and in the integrity of mucosal structure of the intestines.

引用

收藏

页码：1571 / 1574

页数：4

相关论文

共 12 条

[1] FHIT gene therapy prevents tumor development in Fhit-deficient mice [J].

Dumon, KR ;

Ishii, H ;

Fong, LYY ;

Zanesi, N ;

Fidanza, V ;

Mancini, R ;

Vecchione, A ;

Baffa, R ;

Trapasso, F ;

During, MJ ;

Huebner, K ;

Croce, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (06) :3346-3351

[2] Muir-Torre-like syndrome in Fhit-deficient mice [J].

Fong, LYY ;

Fidanza, V ;

Zanesi, N ;

Lock, LF ;

Siracusa, LD ;

Mancini, R ;

Siprashvili, Z ;

Ottey, M ;

Martin, SE ;

Druck, T ;

McCue, PA ;

Croce, CM ;

Huebner, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (09) :4742-4747

[3] Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene [J].

Harada, N ;

Tamai, Y ;

Ishikawa, T ;

Sauer, B ;

Takaku, K ;

Oshima, M ;

Taketo, MM .

EMBO JOURNAL, 1999, 18 (21) :5931-5942

[4] Cancer and the FRA3B/FHIT fragile locus: it's a HIT [J].

Huebner, K ;

Croce, CM .

BRITISH JOURNAL OF CANCER, 2003, 88 (10) :1501-1506

[5]

Ishii H, 2001, CANCER RES, V61, P1578

[6]

Ji L, 1999, CANCER RES, V59, P3333

[7] The FHIT gene, spanning the chromosome 3p14.2 fragile site acid renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers [J].

Ohta, M ;

Inoue, H ;

Cotticelli, MG ;

Kastury, K ;

Baffa, R ;

Palazzo, J ;

Siprashvili, Z ;

Mori, M ;

McCue, P ;

Druck, T ;

Croce, CM ;

Huebner, K .

CELL, 1996, 84 (04) :587-597

[8] LOSS OF APC HETEROZYGOSITY AND ABNORMAL TISSUE BUILDING IN NASCENT INTESTINAL POLYPS IN MICE CARRYING A TRUNCATED APC GENE [J].

OSHIMA, M ;

OSHIMA, H ;

KITAGAWA, K ;

KOBAYASHI, M ;

ITAKURA, C ;

TAKETO, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (10) :4482-4486

[9]

OTTEY M, 2004, IN PRESS BR J CANC

[10] Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in lung and cervical cancer cell lines [J].

Roz, L ;

Gramegna, M ;

Ishii, H ;

Croce, CM ;

Sozzi, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (06) :3615-3620