Home > Research > Publications & Outputs > Suppressor of cytokine signaling 3 (SOCS3) limi...
View graph of relations

Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published

Standard

Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon. / Rigby, R. J.; Simmons, J. G.; Greenhalgh, C. J. et al.
In: Oncogene, Vol. 26, No. 33, 19.07.2007, p. 4833-4841.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

APA

Vancouver

Rigby RJ, Simmons JG, Greenhalgh CJ, Alexander WS, Lund PK. Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon. Oncogene. 2007 Jul 19;26(33):4833-4841. doi: 10.1038/sj.onc.1210286

Author

Bibtex

@article{3ee1d6c4c60a4192baab98db1e7d5aa5,
title = "Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon",
abstract = "Intestinal injury or chronic inflammation induce cytokines that promote crypt regeneration and mucosal repair. If excessive or prolonged, such mechanisms may increase colon cancer risk. Factors that terminate or limit cytokine action in intestinal epithelial cells (IEC) may protect against crypt hyperplasia and neoplasia. We hypothesized that suppressor of cytokine signaling-3 (SOCS3) is such a factor. Mice with Vilin-promoter/Cre-recombinase (VC)mediated IEC-specific SOCS3 gene disruption (VC/HO), WT/HO littermates with floxed but intact SOCS3 genes and VC/WT mice were studied. Colon was examined after acute dextran sodium sulfate (DSS)-induced mucosal injury or after azoxymethane (AOM) and chronic DSS. Signaling pathways were examined in colon, cultured IEC or colon cancer cell lines. VC/HO mice showed no basal phenotype. After acute DSS, VC/HO exhibited enhanced crypt proliferation and crypt hyperplasia and reduced transforming growth factor ( TGF) beta expression in colon. Inflammation and mucosal damage were similar across genotypes. Following AOM/DSS, VC/HO mice had increased size, number and load of colonic tumors and increased STAT3 and nuclear factor-kappa B (NF-kappa B) activation in colon. In vitro, SOCS3 overexpression reduced proliferation, IL-6-mediated STAT3 activation and tumor necrosis factor (TNF) alpha-mediated NF-kappa B activation. We conclude that cytokine induction of SOCS3 normally provides an intrinsic mechanism to limit injury-induced crypt hyperproliferation and inflammation-associated colon cancer by regulating both STAT3 and NF-kappa B pathways.",
keywords = "SOCS3, colon, cancer, mouse model, GROWTH-HORMONE, STAT3 ACTIVATION, TRANSGENIC MICE, CELL-GROWTH, CANCER, HYPERMETHYLATION, CARCINOMA, INACTIVATION, SUPPRESSORS, INHIBITION",
author = "Rigby, {R. J.} and Simmons, {J. G.} and Greenhalgh, {C. J.} and Alexander, {W. S.} and Lund, {P. K.}",
year = "2007",
month = jul,
day = "19",
doi = "10.1038/sj.onc.1210286",
language = "English",
volume = "26",
pages = "4833--4841",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "33",

}

RIS

TY - JOUR

T1 - Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon

AU - Rigby, R. J.

AU - Simmons, J. G.

AU - Greenhalgh, C. J.

AU - Alexander, W. S.

AU - Lund, P. K.

PY - 2007/7/19

Y1 - 2007/7/19

N2 - Intestinal injury or chronic inflammation induce cytokines that promote crypt regeneration and mucosal repair. If excessive or prolonged, such mechanisms may increase colon cancer risk. Factors that terminate or limit cytokine action in intestinal epithelial cells (IEC) may protect against crypt hyperplasia and neoplasia. We hypothesized that suppressor of cytokine signaling-3 (SOCS3) is such a factor. Mice with Vilin-promoter/Cre-recombinase (VC)mediated IEC-specific SOCS3 gene disruption (VC/HO), WT/HO littermates with floxed but intact SOCS3 genes and VC/WT mice were studied. Colon was examined after acute dextran sodium sulfate (DSS)-induced mucosal injury or after azoxymethane (AOM) and chronic DSS. Signaling pathways were examined in colon, cultured IEC or colon cancer cell lines. VC/HO mice showed no basal phenotype. After acute DSS, VC/HO exhibited enhanced crypt proliferation and crypt hyperplasia and reduced transforming growth factor ( TGF) beta expression in colon. Inflammation and mucosal damage were similar across genotypes. Following AOM/DSS, VC/HO mice had increased size, number and load of colonic tumors and increased STAT3 and nuclear factor-kappa B (NF-kappa B) activation in colon. In vitro, SOCS3 overexpression reduced proliferation, IL-6-mediated STAT3 activation and tumor necrosis factor (TNF) alpha-mediated NF-kappa B activation. We conclude that cytokine induction of SOCS3 normally provides an intrinsic mechanism to limit injury-induced crypt hyperproliferation and inflammation-associated colon cancer by regulating both STAT3 and NF-kappa B pathways.

AB - Intestinal injury or chronic inflammation induce cytokines that promote crypt regeneration and mucosal repair. If excessive or prolonged, such mechanisms may increase colon cancer risk. Factors that terminate or limit cytokine action in intestinal epithelial cells (IEC) may protect against crypt hyperplasia and neoplasia. We hypothesized that suppressor of cytokine signaling-3 (SOCS3) is such a factor. Mice with Vilin-promoter/Cre-recombinase (VC)mediated IEC-specific SOCS3 gene disruption (VC/HO), WT/HO littermates with floxed but intact SOCS3 genes and VC/WT mice were studied. Colon was examined after acute dextran sodium sulfate (DSS)-induced mucosal injury or after azoxymethane (AOM) and chronic DSS. Signaling pathways were examined in colon, cultured IEC or colon cancer cell lines. VC/HO mice showed no basal phenotype. After acute DSS, VC/HO exhibited enhanced crypt proliferation and crypt hyperplasia and reduced transforming growth factor ( TGF) beta expression in colon. Inflammation and mucosal damage were similar across genotypes. Following AOM/DSS, VC/HO mice had increased size, number and load of colonic tumors and increased STAT3 and nuclear factor-kappa B (NF-kappa B) activation in colon. In vitro, SOCS3 overexpression reduced proliferation, IL-6-mediated STAT3 activation and tumor necrosis factor (TNF) alpha-mediated NF-kappa B activation. We conclude that cytokine induction of SOCS3 normally provides an intrinsic mechanism to limit injury-induced crypt hyperproliferation and inflammation-associated colon cancer by regulating both STAT3 and NF-kappa B pathways.

KW - SOCS3

KW - colon

KW - cancer

KW - mouse model

KW - GROWTH-HORMONE

KW - STAT3 ACTIVATION

KW - TRANSGENIC MICE

KW - CELL-GROWTH

KW - CANCER

KW - HYPERMETHYLATION

KW - CARCINOMA

KW - INACTIVATION

KW - SUPPRESSORS

KW - INHIBITION

U2 - 10.1038/sj.onc.1210286

DO - 10.1038/sj.onc.1210286

M3 - Journal article

VL - 26

SP - 4833

EP - 4841

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 33

ER -