Reference SummarySchmelz EM, Cancer Res 2001 Sep 15;61(18):6723-9
Title |
Modulation of intracellular beta-catenin localization and intestinal tumorigenesis in vivo and in vitro by sphingolipids. | ||||
Authors |
Schmelz EM; Roberts PC; Kustin EM; Lemonnier LA; Sullards MC; Dillehay DL; Merrill AH Jr | ||||
Journal |
Cancer Res | ||||
Volume |
61 | ||||
Issue |
18 | ||||
Year |
2001 | ||||
Pages |
6723-9 | ||||
Abstract |
Sphingolipid consumption suppresses colon carcinogenesis, but the specific genetic defect(s) that can be bypassed by these dietary components are not known. Colon tumors often have defect(s) in the adenomatous polyposis coli (APC)/beta-catenin regulatory system. Therefore, C57Bl/6J(Min/+) mice with a truncated APC gene product were fed diets supplemented with ceramide, sphingomyelin, glucosylceramide, lactosylceramide, and ganglioside G(D3) (a composition similar in amount and type to that of dairy products) to determine whether tumorigenesis caused by this category of genetic defect is suppressed. Sphingolipid feeding reduced the number of tumors in all regions of the intestine, and caused a marked redistribution of beta-catenin from a diffuse (cytosolic plus membrane) pattern to a more 'normal' localization at mainly intercellular junctions between intestinal epithelial cells. The major digestion product of complex sphingolipids is sphingosine, and treatment of two human colon cancer cell lines in culture (SW480 and T84) with sphingosine reduced cytosolic and nuclear beta-catenin, inhibited growth, and induced cell death. Ceramides, particularly long-chain ceramides, also had effects. Thus, dietary sphingolipids, presumably via their digestion products, bypass or correct defect(s) in the APC/beta-catenin regulatory pathway. This may be at least one mechanism whereby dietary sphingolipids inhibit colon carcinogenesis, and might have implications for dietary intervention in human familial adenomatous polyposis and colon cancer. | ||||
Links |
J:71590 – MGI References 11559543 – National Library of Medicine/PubMed |
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Strain Notes
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon adenoma | Intestine - Large Intestine - Colon |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon adenoma |
|
Intestine - Large Intestine - Colon |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon adenoma |
|
Intestine - Large Intestine - Colon |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon adenoma |
|
Intestine - Large Intestine - Colon |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Distal adenoma | Intestine - Small Intestine - Distal |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Distal adenoma |
|
Intestine - Small Intestine - Distal |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Distal adenoma |
|
Intestine - Small Intestine - Distal |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Distal adenoma |
|
Intestine - Small Intestine - Distal |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Medial adenoma | Intestine - Small Intestine - Medial |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Medial adenoma |
|
Intestine - Small Intestine - Medial |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Medial adenoma |
|
Intestine - Small Intestine - Medial |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Medial adenoma |
|
Intestine - Small Intestine - Medial |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Proximal adenoma | Intestine - Small Intestine - Proximal |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Proximal adenoma |
|
Intestine - Small Intestine - Proximal |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Proximal adenoma |
|
Intestine - Small Intestine - Proximal |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine - Proximal adenoma |
|
Intestine - Small Intestine - Proximal |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine adenoma | Intestine |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine adenoma |
|
Intestine |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine adenoma |
|
Intestine |
observed |
|
| C57BL/6J-ApcMin/+ | Intestine adenoma |
|
Intestine |
observed |