Estrogens regulate the expression of NHERF1 in normal colon during the reproductive cycle of Wistar rats

Abstract

In breast cancer cell lines, the Na(+)/H(+) exchanger regulator factor 1 (NHERF1) gene is regulated at the transcriptional level by estrogens, the protein expression levels correlate with the presence of estrogen receptors and the effect is blocked by anti-estrogens. However, there is limited information regarding the regulation of NHERF1 by estrogens in normal colon tissue. The NHERF1 protein has an important role in the maintenance of the intestine ultrastructure. NHERF1-deficient mice showed defects in the intestinal microvilli as well as molecular alterations in brush border membrane proteins. Here, we have studied the expression of NHERF1 in normal rat colon and uterus during the reproductive cycle of Wistar rats. We found that NHERF1 expression in rat colon during the estral cycle is modified by estrogen levels: higher expression of NHERF1 was observed during the proestrous and estrous stages and lower expression in diestrous 1 when estrogen levels decreased. In uterus, NHERF1 was expressed in the apical region of the luminal epithelium and glands in all stages of the estral cycle, and in both colon and uterus, the expression was independent of the proliferation status. Our results show that NHERF1 expression is regulated by estrogens in colon during the rat estral cycle.

NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia

“…The tumor density was increased in female mice of both genotypes, whereas adenomas developed at a similar rate in both genders in Apc Min/+ mice and yet again with female predominance in Apc Min/+ NHERF1 −/− double-mutant mice. One correlation is the regulation of NHERF1 expression by estrogen receptor [47] and its variation in rodent intestine during estral cycle [48]. Although this could explain the limited growth of adenomas in Apc Min/+ females by a suppressor effect of NHERF1, more studies are necessary to address the increased tumor incidence in Apc Min/+ females.…”

Expression of NHERF1 in Colonic Tumors Induced by 1,2-dimethylhydrazine in Rats is Independent of Plasma Ovarian Steroids

“…In the positive carcinoma cases, the expression of NHERF1 was mainly cytoplasmic as was previously described for breast cancer cell lines [24]. NHERF1 expression is stimulated by estrogens in breast cancer cells and normal colon tissue; however, its regulation by estrogens in colon cancer is still unknown [8,28]. Here, we tested the hypothesis that NHERF1 could act as a tumor suppressor gene in colon cancer as a mediator of the estrogens' protective actions in colon carcinogenesis.…”

“…In normal rat colon, the expression of NHERF1 fluctuates during the estral cycle in response to E2 levels in plasma indicating the regulation of NHERF1 by estrogens in this tissue [8]. A recent report in human samples describes the absence of NHERF1 expression in human adenomas and the ectopic cytoplasmic expression of NHERF1 in about 50% of human adenocarcinoma specimens [24].…”

“…In normal rat colon, NHERF1 protein is expressed in the apical membrane of the epithelial cells and the levels fluctuate with plasmatic estrogens during the reproductive cycle of the rat [8]. In order to understand the estrogenic regulation of NHERF1 in transformed colon epithelium, we analyzed the expression of NHERF1 in tumors from intact (ten) and ovariectomized (seven) rats by immunohistochemistry.…”

Histochemistry and cell biology: the annual review 2010

“…Due to observations that NHERF1 may act as a tumour suppressor or as oncogene (Pan et al 2006;Shibata et al 2003) and that treatment with estrogens prevents colon carcinogenesis, a potential role of NHERF1 in colon carcinogenesis needed to be determined. Cuello-Carrion et al (2010), therefore used the colon and uterus of cycling rats to study NHERF1 expression during the estral cycle. During the estrous stage the authors found oestrogen-dependent expression of NHERF1 in the colon.…”