Antisteroidal compounds and steroid withdrawal down-regulate cadherin-11 mRNA and protein expression levels in human endometrial stromal cells undergoing decidualisation in vitro

Abstract

The cellular mechanisms by which steroids and antisteroidal compounds modulate the function and/or integrity of the human endometrium remain poorly understood. We recently determined that the expression of the novel cadherin subtype, known as cadherin‐11, is tightly regulated in endometrial stromal cells undergoing decidualisation in vivo and in vitro. To determine whether the actions of antisteroids on the endometrium are mediated, at least in part, by their ability to regulate the expression of this cell adhesion molecule, we examined the effects of the antiprogestin RU486 and the antiestrogen ICI 182,780 on cadherin‐11 mRNA and protein expression levels in human endometrial stromal cells undergoing decidualisation in vitro. RU486 decreased the levels of the cadherin‐11 mRNA transcript and protein species present in these cell cultures in a dose‐ and time‐dependent manner. Similarly, ICI 182,780 was capable of reducing stromal cadherin‐11 mRNA and protein expression levels in a dose‐dependent manner, suggesting that the progesterone‐mediated increase in cadherin‐11 expression levels in human endometrial cells undergoing decidualisation in vitro is dependent on the presence of estrogens. Cadherin‐11 expression levels also were reduced in endometrial stromal cell cultures subjected to progesterone withdrawal, an in vitro model for menstrual breakdown. These studies not only give us useful insight into the mechanism(s) by which progesterone regulates stromal cadherin‐11 expression, but they strengthen our hypothesis that this cell adhesion molecule plays a central role in the remodeling processes that occur in the human endometrium in response to fluctuations in the levels of gonadal steroids. Mol. Reprod. Dev. 53:384–393, 1999. © 1999 Wiley‐Liss, Inc.

Sodium/potasium ATPase (Na+, K+-ATPase) and ouabain/related cardiac glycosides: a new paradigm for development of anti- breast cancer drugs?

“…They found that progesterone, but not E2 or dihydroestosterone, was capable of regulating Cad-11 expression. However, E2 was capable of potentiating the stimulating effects of progesterone in a dose-dependent manner [172,173], and that the antiestrogen, ICI182780, was capable of reducing Cad-11 expression in these cells, suggesting the requirement of estrogens and ERs in mediating these effects [174]. Gorodeski [175] studied the effects of estrogens and aging on paracellular permeability of human vaginal-cervical epithelia by determining the transepithelial electrical conductance (TEC) across cultures of normal human ectocervical epithelial cells on filters.…”

“…if it is involved inhibition of E2-Induced activation of MAPK pathway; Second, both ERs [188][189][190] and Na + , K + -ATPase [117,142,191] are known to be involved in the regulation of NF-jB, a pleiotropic transcriptional factor involved in the regulation of diverse biological processes such as apoptosis, cell survival, cell growth and cell division in normal and various cancers including breast cancer [192][193][194]. It will be also interesting to determine if ouabain is involved in the regulation of both ER-and Na + , K + -ATPase-mediated regulation of NF-jB in breast cancer cells; Third, both ERs [174,177] and Na + , K + -ATPase [43,55,61,76,84] are known to play key role in the regulation of TJs and AJs. Aberrant (usually reduced or loss) expression of various components of TJs and AJs has been frequently observed in breast cancer cells [70,87,98].…”

“…Aberrant (usually reduced or loss) expression of various components of TJs and AJs has been frequently observed in breast cancer cells [70,87,98]. E2 suppresses, directly or indirectly, the expression of several groups of components of TJs and AJs [172][173][174]176,195,196]. These effects could be particularly important in human breast cells, since they are exposed to relatively high E 2 levels due to the in situ E 2 synthesis by local aromatase activity [22][23][24]26].…”

P-Cadherin Is Up-Regulated by the Antiestrogen ICI 182,780 and Promotes Invasion of Human Breast Cancer Cells

“…Because aberrant expression of P-cadherin identified a subgroup of estrogen receptor-␣-negative breast carcinomas (16), we raised the hypothesis that the expression of P-cadherin in mammary epithelial cells is hormonally regulated, as described for E-cadherin (20), Ncadherin (21), and cadherin-11 (22).…”

Estradiol Promotes M1-like Macrophage Activation through Cadherin-11 To Aggravate Temporomandibular Joint Inflammation in Rats

“…Furthermore, cadherin-11 is also expressed in the alveolar macrophages of patients with pulmonary fibrosis (24). Meanwhile, estradiol can regulate cadherin-11 expression in human endometrial stromal cells (25,26) and in neurons of macaques (27). Therefore, we further hypothesized that estrogen might promote M1/M2 macrophage polarization through potentiating cadherin-11 to aggravate joint inflammation.…”