Effects of the oestrogen receptor antagonist Fulvestrant on expression of genes that affect organization of the epididymal epithelium.

The role of oestrogens in epididymal function is still unclear. Knockout of the oestrogen receptor ESR1 (Esr1(-/-) ) or treatment with the anti-oestrogen Fulvestrant affect epididymal milieu and sperm motility. We investigated the effect of in vivo treatment of rats with Fulvestrant on: (i) expression of genes that may be important for the architecture and function of the epididymal epithelium: prominins 1 and 2, metalloproteinase 7, claudin 7, beta-catenin and cadherin 13, and (ii) levels of oestradiol and testosterone, and expression of oestrogen and androgen receptors, in the initial segment (IS), caput, corpus and cauda epididymis. Fulvestrant (i) reduced gene expression of prominin 1 (variant 1) in the caput, reduced prominin 1 protein content in the caput epididymis and in the efferent ductules, and increased the localization of prominin 1 in microvilli of the caput and corpus; (ii) reduced gene expression of prominin 2 in the corpus and cauda epididymis; (iii) increased the metalloproteinase 7 content in the apical region of principal cells from IS/caput; (iv) reduced in the corpus epididymis, but increased in the efferent ductules, the cadherin 13 mRNA level; (v) reduced testosterone but increased oestradiol levels in the corpus and cauda; (vi) increased the androgen receptor protein content in all regions of the epididymis, and the oestrogen receptor GPER in the corpus and cauda epididymis. In conclusion, treatment with Fulvestrant induced regional-specific changes in hormonal and steroid receptor content, and affected expression of proteins important for epithelial organization and absorption/secretion. The mechanisms of oestrogen action may differ among epididymal regions, which may contribute to determine region-specific sperm functions.

Matrilysins may not predict the metastatic potential in squamous cell carcinoma of the tongue.

OBJECTIVE: To examine immunoexpression of matrix metalloproteinase (MMP)-7 and -26 in squamous cell carcinoma (SCC) of the tongue and its relation with cervical metastasis. MATERIAL AND METHODS: Twenty-four cases were selected and divided into two groups: a metastatic group (n = 12) and a non-metastatic group (n = 12). Cases were graded as either negative (score 0), positive (score +) or strongly positive (score ++). RESULTS: MMP-7 expression was identical in both groups, with 17% of the cases graded as score 0, 50% as score + and 33% as score ++. MMP-26 expression was 25% score 0, 8% score + and 67% score ++ in the metastatic group, and 8% score 0, 50% score + and 42% score ++ in the non-metastatic group. Statistical analysis showed no differences between the studied groups and no correlations between proteins. CONCLUSIONS: MMP-7 and -26 immunostaining is not a useful indicator of the metastatic potential of SCCs of the tongue. However, the role of these proteins in the process of invasion and metastasis cannot be ruled out since their more marked presence along the tumor invasion front compared to more central areas of the tumors indicates higher secretion of these proteases in this region, facilitating the invasion process.

Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts.

OBJECTIVE: The objective of this study was to analyze the expression of matrix metalloproteinases (MMPs) 1, 7, and 26 in odontogenic keratocysts (OKCs) associated with Gorlin syndrome (SOKCs) and nonsyndrome OKCs (NSOKCs). STUDY DESIGN: Twenty-one SOKCs and 20 NSOKCs were evaluated for epithelial expression of MMP-1, MMP-7, and MMP-26 and for mesenchymal expression of MMP-1 by immunohistochemistry. RESULTS: Strong epithelial positivity to MMP-1 was observed in 76% of SOKCs and in 15% of NSOKCs (P < .05). Strong mesenchymal immunoreactivity to MMP-1 was observed in 38% of SOKCs and in 20% of NSOKCs (P > .05). Epithelial immunoreactivity to MMP-7 was strongly positive in 67% of SOKCs and in 40% of NSOKCs (P > .05). For MMP-26, strong positivity was found in 62% of SOKCs, in contrast to 35% of NSOKCs (P > .05). CONCLUSION: MMPs-1, -7 and -26 may play important roles in the biology of OKCs. Furthermore, the presence of these proteases at higher levels in SOKCs may help to explain increased OKC aggressiveness associated with nevoid basal cell carcinoma syndrome.