Co-ordinated expression of connexins 26 and 32 in human endometrial glandular epithelium during the reproductive cycle and the influence of hormone replacement therapy

Saito, Tsuyoshi; Oyamada, Masahito; Yamasaki, Hiroshi; Mori, Makoto; Kudo, Ryuichi

doi:10.1002/(sici)1097-0215(19971114)73:4<479::aid-ijc4>3.0.co;2-x

Cited by 21 publications

(9 citation statements)

References 17 publications

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“…Consequently, it may be suggested that activation of PR by progesterone could prevent accumulation of dysfunctional Cx26 in the cytoplasm, which may confirm previous studies. 13,14 Our study showed accumulation of Cx26 expression predominantly in the cytoplasm of cancerous cells, which could mark storage of dysfunctional protein. Therefore, negative correlation between Cx26 and PR may partially support this hypothesis.…”

Section: Discussionmentioning

confidence: 74%

“…In contrast to these findings, working on the effect of steroid hormones on the Cx expression in endometrium of rats, Risek et al 13 showed that progesterone could be a positive regulator of the Cx expression. Furthermore, Saito et al, 14 who studied the expression of Cx26 and Cx32 in human endometrial glandular epithelium during the reproductive cycle as well as the influence of hormone replacement therapy on Cx expression, demonstrated that expression of both Cxs was controlled by serum progesterone. Expression of Cx26 and Cx32 altered significantly during the menstrual cycle: weak expression in the proliferative phase, markedly elevated during ovulation, and most pronounced in the midYsecretory phase.…”

Section: Discussionmentioning

confidence: 99%

“…14 Consequently, it was concluded that these Cxs were suppressed in the presence of estrogen alone but up-regulated in the presence of both progesterone and estrogen. 14 Little is known about correlations between sex steroids and GJIC in endometrial cancer. It is important to note that only in the study of Saito et al 21 it has been reported about the impact of estrogen and its receptor on Cx26 and Cx32 expression in endometrial carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

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Comparative Evaluation of Estrogen and Progesterone Receptor Expression With Connexins 26 and 43 in Endometrial Cancer

Lesniewicz

Kańczuga‐Koda

Baltaziak

et al. 2009

International Journal of Gynecological Cancer

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Progression of numerous neoplasms could involve alterations of gap junction channels composed of connexins (Cxs). Disorders of expression and cellular displacement of Cxs were also found in endometrial cancer. Gap junctional intercellular communication can be regulated by wide array of agents, for instance, growth factors, oncogenes, and steroid hormones. Nevertheless, expressions of Cxs and progesterone receptor (PR) were not compared in human tissues. This study focused on assessment of expression of estrogen receptor alpha (ERalpha) and PRs in relation to the expression of Cx26 and Cx43 in 88 cases of endometrial cancer and analysis of these proteins' expression in comparison with anatomoclinical features. Positive ERalpha and PR nuclear staining was present in 66 (75%) and 60 (68.2%) of all studied tumors, respectively. Positive correlation was found between expression of PR and histopathologic type of tumor (P = 0.026), and negative correlation was drawn with grading (G) (P = 0.002). There were positive reactions to Cx26 and Cx43 of mainly cytoplasmic location in 60 (68.2%) and 66 (75%) of studied cancers, respectively. Progesterone receptor expression correlated negatively with Cx26 in endometrial cancers (P = 0.016, r = -0.256). Moreover, ERalpha expression positively correlated with PR expression (P < 0.001, r = 0.678). On the ground of our findings, disorders of Cx expression and altered distribution pattern occur during endometrial carcinogenesis, and it seems that PR could participate in this fact. Loss of functional gap junctions may occur because of the aberrant expression and localization of Cx26 and Cx43 in endometrial cancer.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparative Evaluation of Estrogen and Progesterone Receptor Expression With Connexins 26 and 43 in Endometrial Cancer

Lesniewicz

Kańczuga‐Koda

Baltaziak

et al. 2009

International Journal of Gynecological Cancer

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“…Gap junctions in the human endometrial epithelial cells were shown to consist of Cx26 and Cx32 [44,45,46]. An increasing intensity of Cx26 staining was observed in the uterine epithelial cells during the course of the proliferative phase, but it could hardly be detected in the secretory phase, including the receptive window.…”

Section: Cell–cell Junctions In the Cyclic Human Endometriummentioning

confidence: 99%

“…An increasing intensity of Cx26 staining was observed in the uterine epithelial cells during the course of the proliferative phase, but it could hardly be detected in the secretory phase, including the receptive window. For Cx32, a weak expression could be observed at the basal portion of the epithelial cells which decreased during the receptive phase [44], whereas other studies demonstrated an increase of Cx32 in the early secretory and a decrease in the late secretory phase [46]. In contrast to tight and adhesion junctions, gap junctions are also present in the endometrial stromal cells.…”

Section: Cell–cell Junctions In the Cyclic Human Endometriummentioning

confidence: 99%

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

Grund

Grümmer

2018

IJMS

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Cell contacts exhibit a considerable influence on tissue physiology and homeostasis by controlling paracellular and intercellular transport processes, as well as by affecting signaling pathways. Since they maintain cell polarity, they play an important role in cell plasticity. The knowledge about the junctional protein families and their interactions has increased considerably during recent years. In contrast to most other tissues, the endometrium undergoes extensive physiological changes and reveals an extraordinary plasticity due to its crucial role in the establishment and maintenance of pregnancy. These complex changes are accompanied by changes in direct cell–cell contacts to meet the various requirements in the respective developmental stage. Impairment of this sophisticated differentiation process may lead to failure of implantation and embryo development and may be involved in the pathogenesis of endometrial diseases. In this article, we focus on the knowledge about the distribution and regulation of the different junctional proteins in the endometrium during cycling and pregnancy, as well as in pathologic conditions such as endometriosis and cancer. Decoding these sophisticated interactions should improve our understanding of endometrial physiology as well as of the mechanisms involved in pathological conditions.

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Nuclear localization of ?-catenin in normal and carcinogenic endometrium

et al. 1999

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We have previously shown that the connexin (Cx) 26 and 32 genes are expressed during the secretory phase of the human endometrium and that their expression is downregulated during the proliferative phase, suggesting a role for intercellular transduction in cell growth control in human endometrium. To further study the possible role of cell-to-cell interaction in growth regulation, we immunohistochemically analyzed 80 endometrial samples (30 of normal endometrium, 20 of endometrial hyperplasia, and 30 of endometrial cancer) for the expression of E-cadherin; alpha-, beta-, and gamma-catenin; adenomatous polyposis coli (APC) protein, and sex-steroid hormone receptors at three points in the cells: the cell-to-cell border, the cytoplasm, and the nucleus. In this study, moderate or strong staining of beta-catenin in the nuclei was observed in 60.0% of endometrial hyperplasia samples and 30.0% of endometrial cancer samples, although the beta-catenin gene was mutated in only two of the nine samples that showed the intensive nuclear staining. Western blotting analysis showed that the samples that had intense nuclear staining of beta-catenin had much higher expression of beta-catenin than the samples that did not have nuclear staining. Furthermore, normal endometrium showed nuclear localization, especially in the mid- and late-proliferative and early-secreting phases of the menstrual cycle. The results suggest that the nuclear localization of beta-catenin observed in endometrial hyperplasia and endometrial cancer, as in other tumors, implies that beta-catenin/Wnt-1 signal transduction is highly activated in carcinogenesis of the endometrium as well as in normal physiological conditions.

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Co-ordinated expression of connexins 26 and 32 in human endometrial glandular epithelium during the reproductive cycle and the influence of hormone replacement therapy

Cited by 21 publications

References 17 publications

Comparative Evaluation of Estrogen and Progesterone Receptor Expression With Connexins 26 and 43 in Endometrial Cancer

Comparative Evaluation of Estrogen and Progesterone Receptor Expression With Connexins 26 and 43 in Endometrial Cancer

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

Nuclear localization of ?-catenin in normal and carcinogenic endometrium

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