マウスにおける大腸がんのAOM/DSSモデルにおけるサルコ/小胞体カルシウムATPaseの発現

The expression of different sarco/endoplasmic reticulum calcium ATPase (SERCA) isoforms is controversial in various cancers and is not clear in the experimental cancer model. The present study attempts to evaluate the expression dynamics of SERCA isoforms in the azoxymethane/dextran sulphate sodium salt (AOM/DSS) model of colorectal carcinogenesis in mice. Inflammation-associated colorectal cancer was induced in the mice by administration of a single dose of AOM and three alternative cycles of DSS in drinking water. Body weights were recorded weekly. Mice were killed at weeks 0, 8, 12 and 16. At those times, the number of tumours was recorded, and colon tissues were processed for histopathological, immunohistochemical and gene expression analysis. The number of tumours and the formation of aberrant crypt foci were found to be significantly higher in the AOM/DSS group compared to the control. Histopathology of the colon revealed a higher percentage of dysplasia, adenoma and adenocarcinoma formation in the AOM/DSS group, further supported by high intensity of immunohistochemical staining for PCNA in the same. Gene expression analysis indicated higher expression of cyclin D1, β-catenin and low expression of E-cadherin, suggesting carcinogenic transformation of the colon. Immunohistochemical and gene expression analysis of SERCA isoforms indicated higher expression of SERCA1 and SERCA2 and low expression of SERCA3 in colon tissues of the AOM/DSS-exposed animals. The present study confirmed a similar expression pattern of SERCA isoforms in the AOM/DSS model of carcinogenesis as reported in clinical samples. Further, this study highlights the fact that altered SERCA patterns could be a contributing factor in the development of colorectal carcinogenesis.