In Nonfunctional Pituitary Adenomas, Estrogen Receptors and Slug Contribute to Development of Invasiveness

Context: Clinical studies suggest that an imbalance in the actions of estrogen receptor (ER)-alpha and ER beta is associated with invasion of tumors of epithelial origin. Both ER have been detected in the pituitary adenomas (PA). Our previous study together with other reports suggests that an imbalance between ER alpha and ER beta contributes to the pathogenesis and biological behavior of PA including invasion. However, the roles of the two ER in invasiveness of PA have not been clarified. Objective: The expression of ER, Slug, and E-cadherin in 41 cases of nonfunctional PA (NFPA) were determined to evaluate whether ER were related to the invasiveness of NFPA. Furthermore, we aimed by analysis of the correlation between ER and E-cadherin or Slug to understand molecular mechanisms related to invasiveness. Methods: Immunohistochemistry, RT-PCR, and Western blot were performed. Results: Nuclear ER alpha staining was significantly stronger in invasive NFPA than noninvasive ones (P < 0.01). In contrast, nuclear ER beta staining was significantly weaker in invasive NFPA than in noninvasive ones (P < 0.01). Both E-cadherin mRNA and protein were decreased in invasive NFPA compared with noninvasive ones. Moreover, Slug, a repressor of E-cadherin, was significantly increased in invasive over noninvasive NFPA (P < 0.01). There were significant correlations between ER and Slug or E-cadherin in NFPA, in which Slug was positively correlated with ER alpha and inversely correlated with ER beta, whereas E-cadherin was positively correlated with ER beta and inversely correlated with ER alpha. Conclusions: ER alpha and ER beta may act in opposite directions to regulate the Slug-E-cadherin pathway and to affect invasiveness of NFPA. (J Clin Endocrinol Metab 96: E1237-E1245, 2011)