Unremitting Cell Proliferation in the Secretory Phase of Eutopic Endometriosis: Involvement of pAkt and pGSK3β

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This study investigated eutopic endometrium from women with and without endometriosis, finding elevated Ki67 and SCF in endometriosis, particularly in the secretory phase, with increased pAkt and pGSK3β in endometriosis secretory endometrium.

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This study analyzed eutopic endometrium from 35 women with endometriosis and 25 fertile controls with normal cycles, using in situ expression measurements across menstrual phases for SCF/c-kit, Ki67, Akt/GSK3β, and their phosphorylated forms. Ki67 and SCF expression were higher in endometriosis than controls and were greater in the secretory phase rather than the proliferative phase, while c-kit expression was also higher overall but did not differ by phase. In contrast, total Akt and GSK3β levels were identical across all samples, but phosphorylated Akt and phosphorylated GSK3β remained overexpressed in the secretory phase in endometriosis compared with control tissue. The authors’ main limitation is that this is an expression-based, in situ analysis without functional experiments to prove causality. This paper is centrally about endometriosis — it investigates how c-kit/SCF and pAkt/pGSK3β signaling relate to unremitting cell proliferation in the secretory phase of eutopic endometriosis.

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Abstract

ObjectiveEndometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium.DesignEutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle.ResultsExpression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis.ConclusionUnceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways.
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Abstract

Objective Endometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium. Design Eutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle.

Results

Expression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis.

Conclusion

Unceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways. Similar content being viewed by others

References

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Unremitting Cell Proliferation in the Secretory Phase of Eutopic Endometriosis: Involvement of pAkt and pGSK3β. Reprod. Sci. 22, 502–510 (2015). https://doi.org/10.1177/1933719114549843 Published: Issue date: DOI: https://doi.org/10.1177/1933719114549843

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endometriosis

MeSH descriptors

Cell Proliferation Endometriosis Endometrium Glycogen Synthase Kinase 3 Proto-Oncogene Proteins c-akt Adult Biopsy Case-Control Studies Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Glycogen Synthase Kinase 3 Glycogen Synthase Kinase 3 beta Humans Immunohistochemistry Ki-67 Antigen

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