The MUC5AC IRS was significantly higher in mutated Gr-LSTs compared to non-mutated tumors (1.2 �� 1.3 vs 0.2 �� 0.6, P < 0.05). No significant differences were found in other IRSs (data not shown). selleck chem Seliciclib DISCUSSION Only a few reports are available on the phenotypic expression of gastrointestinal cell lineage with immunohistochemistry of MUC2, MUC5AC, MUC6 and CD10 in relation to colorectal adenoma-carcinoma sequence[24-26]. In proximal colon lesions, MUC5AC expression was significantly higher in Gr-LSTs than NGr-LSTs. Expression of MUC5AC or HGM was increased in adenoma with villous histology or polypoid growth[21,24,25]. Enhanced MUC6 immunoreactivity was reported to be exhibited in large adenomas[21]. In the current study, MUC6 was expressed only in NGr-LSTs, suggesting it as a marker of a morphologically distinct tumor.
The molecular mechanisms responsible for the aberrant expression of gastric mucin, MUC5AC and MUC6 in colorectal tumors are still unclear and may be due to changes in transcriptional regulation. It was previously reported that none of the four NGr-LSTs harbored p53 mutations, whereas 7 out of 24 (29%) Gr-LSTs were positive[16]. We have shown that no significant differences in p53 expression, along with an inverse relation of p53 to MUC2 or MUC5AC expression in two types of LSTs. An experimental study identified MUC2 expression as increased along with induction of wild-type p53 in carcinoma cell lines in vitro, and potential p53-binding sites in the MUC2 promoter, which contributes to stimulation of promoter activity[29].
P53 overexpression as an indirect sign of loss of functional p53 by its mutation is possibly related to the down-regulation of MUC2 expression in colorectal LST. A detailed study on the relation of p53 to the altered mucin expression appears warranted. We have documented high nuclear ��-catenin expression in NGr-LSTs in line with a previous study[15]. In an analysis of LSTs, no mutation of ��-catenin exon 3 was found, while LOH at 5q (APC locus) was more frequently detected in NGr-LSTs than in Gr-LSTs[12]. To date, there is only one case report of NGr-LST harboring interstitial deletion of ��-catenin exon 3[13]. Nuclear accumulation of ��-catenin has been observed in tumors with mutations in the ��-catenin or APC gene[3]. Taken together, the available data suggest that activation of Wnt/APC/��-catenin signaling in NGr-LSTs is due primarily to alterations in the APC gene.
Furthermore, inverse associations were shown between nuclear ��-catenin and MUC2 or MUC5AC in LSTs. Experimental studies have demonstrated that abrogation of MUC2 in tumors of the rat colon is related to nuclear ��-catenin localization and its mutation[30,31]. Interaction of mucin core protein with Carfilzomib Wnt/APC/��-catenin signaling may have some role in the progression of LSTs.
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