The Interleukin-6 Family Cytokine Interleukin-11 Regulates Homeostatic Epithelial Cell Turnover and Promotes Gastric Tumor Development

被引：85

作者：

Howlett, Meegan ^{[1
,2
]}

Giraud, Andrew S. ^{[1
]}

Lescesen, Helen ^{[1
]}

Jackson, Cameron B. ^{[1
,2
]}

Kalantzis, Anastasia ^{[2
]}

Van Driel, Ian R. ^{[3
]}

Robb, Lorraine ^{[4
]}

Van der Hoek, Mark ^{[5
]}

Ernst, Matthias ^{[6
]}

Minamoto, Toshinari ^{[7
]}

Boussioutas, Alex ^{[8
]}

Oshima, Hiroko ^{[7
]}

Oshima, Masanobu ^{[7
]}

Judd, Louise M. ^{[1
,2
]}

机构：

[1] Murdoch Childrens Res Inst, GRIP Lab, Parkville, Vic, Australia

[2] Univ Melbourne, Dept Pediat, Melbourne, Vic, Australia

[3] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Dept Biochem & Mol Biol, Melbourne, Vic, Australia

[4] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

[5] Univ Adelaide, Adelaide Microarray Ctr, Adelaide, SA, Australia

[6] Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia

[7] Kanazawa Univ, Canc Res Inst, Kanazawa, Ishikawa 920, Japan

[8] Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia

来源：

GASTROENTEROLOGY | 2009年 / 136卷 / 03期

关键词：

HELICOBACTER-PYLORI; CORECEPTOR GP130; GENE-EXPRESSION; CARCINOMA CELLS; IL-11; RECEPTOR; CANCER CELLS; BETA-SUBUNIT; MUTANT MICE; PROTEIN; GROWTH;

D O I：

10.1053/j.gastro.2008.12.003

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Gastric cancer is the second most common cause of cancer-related mortality worldwide, mainly as a result of late-stage detection. Interleukin (IL)-11 is a multifunctional cytokine reported to be up-regulated in human gastric cancer. Methods: We investigated the importance of IL-11 in gastric cancer progression by examining its role in a variety of mouse gastric tumor models, as well as in nonneoplastic and tumor tissues taken from gastric cancer patients. We then determined the transcriptional and translational outcomes of IL-11 overexpression in normal gastric mucosa and identified a novel gene signature important early in the progression toward gastric tumorigenesis. Results: IL-11 was up-regulated significantly in 4 diverse mouse models of gastric pathology as well as m human biopsy specimens adjacent to and within gastric cancer. Removal of IL-11 co-receptor a significantly reduced HK beta-/- mouse fundic hyperplasia and ablated gp130(757F/F) mouse tumorigenesis. Exogenous IL-11 but not IL,6 activated oncogenic signal transducer and activator of transcription-3, and altered expression of novel proliferative and cytoprotective genes RegIII-beta, RegIII-gamma, gremlin-1, clusterin, and growth arrest specific-1 in wild-type gastric mucosa, a gene signature common in gp130(757F/F) and HK beta-/- tumors as well as nonneoplastic mucosa of gastric cancer patients. One week of chronic IL-11 administration in wild-type mice sustained the gene signature, causing pretumorigenic changes in both antrum and fundus. Conclusions: Increased gastric IL-11 alters expression of proliferative and cytoprotective genes and promotes pretumorigenic cellular changes.

引用

页码：967 / 977

页数：11

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