Expression of uteroglobin and matrix metalloproteinase-9 genes in endometrial cancer: Relationship to estrogen and progesterone receptor status

Abstract

Uteroglobin (UG) is a protein expressed in secretory epithelia of different tissues, including the human endometrium, where the expression levels are modulated by ovarian steroids. There is evidence that UG, which is a potent inhibitor of the activity of phospholipases A2, has anti-proliferative effects and we have previously demonstrated that enforced UG expression reverts the transformed phenotype in the endometrial cancer cell line HEC-1A. The objective of the present study was to evaluate the expression of UG in endometrial cancer tissues. Furthermore, the estrogen (ER) and progesterone (PR) receptor status was investigated. Finally, the amount of expression of matrix metalloproteinase-9 (MMP-9), which is stimulated by estrogens, was determined. Twenty-five patients were included in the study. Total RNA was extracted from tissue samples obtained at surgery. UG, ERalpha, ERbeta, PR transcripts were analyzed by RT-PCR both in tissues and in different endometrial cancer cell lines. The levels of MMP-9 and of the tissue inhibitor of matrix-metalloproteinase-1 (TIMP-1) mRNA were determined by real-time RT-PCR. The statistical analysis of the results was based on Chi-square and t-test. UG expression was found in 73% of cases. No difference in the histopathological features between tumors expressing or not expressing UG was observed. The presence of UG significantly correlated with the expression of ERalpha and PR. The amount of MMP-9 was higher in UG+ and ERalpha+ tumors. Similar correlations were found in cell lines. Thus, our results indicate that the presence of UG in the majority of cases of endometrial carcinoma that were investigated, hypothetically a favorable disease marker, appears to be counteracted by high levels of MMP-9 expression.