An essential role of p27 downregulation in fenvalerate-induced cell growth in human uterine leiomyoma and smooth muscle cells

Gao, Xiaohua; Yu, Linda Chia‐Hui; Castro, Lysandra; Tucker, Charles J.; Moore, Alicia B.; Xiao, Hang; Dixon, Darlene

doi:10.1152/ajpendo.00107.2012

Cited by 10 publications

(13 citation statements)

References 29 publications

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“…With the exception of these values, the median for quantification of Ki-67-positive cells in UPA-treated myomas was also low, tending to be lower than in untreated myomas, particularly in the UPA5 group, but with no statistically significant difference. Indeed, dysregulations in expression of cyclin-dependent kinase or cycle regulators have already been investigated and reported in myomas (36,37). Among them, cyclindependent inhibitor p27 controls growth of myoma cells (37,38), while cyclin-dependent kinase 2 has been shown to be involved in growth inhibition of myoma cells treated with SPRMs (39).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, dysregulations in expression of cyclin-dependent kinase or cycle regulators have already been investigated and reported in myomas (36,37). Among them, cyclindependent inhibitor p27 controls growth of myoma cells (37,38), while cyclin-dependent kinase 2 has been shown to be involved in growth inhibition of myoma cells treated with SPRMs (39). It would therefore be very interesting to determine whether UPA could regulate these proteins.…”

Section: Discussionmentioning

confidence: 99%

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In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment

Courtoy

Donnez

Marbaix

et al. 2015

Fertility and Sterility

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment

Courtoy

Donnez

Marbaix

et al. 2015

Fertility and Sterility

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“…Aspirin inhibits cell proliferation in human uterine leiomyoma cells. Human uterine leiomyoma (UtLM) cells (GM10964) obtained from Coriell Institute for Medical Research have been used widely for investigating cell proliferation of uterine leiomyoma in research as in vitro modeling system (27,28). Therefore, we used this cell line for investigating the effects of aspirin on uterine leiomyoma.…”

Section: Resultsmentioning

confidence: 99%

Aspirin inhibits the proliferation of human uterine leiomyoma cells by downregulation of K-Ras-p110α interaction

et al. 2017

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Aspirin has been confirmed as an effective antitumor drug in various cancers. However, the relationship between aspirin and uterine leiomyoma is still underexplored. Here, we explored the effects of aspirin on human uterine leiomyoma cells and provide insights into the underlying mechanisms. Cell Counting Kit-8 (CCK-8) and flow cytometry analysis showed that aspirin treatment inhibited cell proliferation and promoted cell cycle arrest at G0/G1 phase in a dose- and time‑dependent manner of human uterine leiomyoma cells. Further studies revealed that aspirin blocked the interaction between K-Ras and p110α by co-immunoprecipitation and immunofluorescence. Western blotting demonstrated K‑Ras‑p110α interaction was required for the effects of aspirin‑induced inhibition on cell growth and cell cycle transition via cell cycle regulators, including cyclin D1 and cyclin-dependent kinase 2 (CDK2). PI3K/Akt/caspase signaling pathway was involved in human uterine leiomyoma cell growth under aspirin treatment. Taken together, these results suggest that aspirin inhibited human uterine leiomyoma cell growth by regulating K‑Ras‑p110α interaction. Aspirin which targeting on interaction between K-Ras and p110α may serve as a new therapeutic drug for uterine leiomyoma treatment.

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“…In addition, transfection of LSMCs with cyclin G1 antisense oligos led to increased expression of both p21 and p27 cyclin-dependent kinase inhibitors and induction of apoptosis [64]. Leiomyoma cells also showed increased proliferation in response to fenvalerate due to down-regulation of the cyclin inhibitor p27 compared to normal uterine myometrial cells [65]. …”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix Collagen Alters Cell Proliferation and Cell Cycle Progression of Human Uterine Leiomyoma Smooth Muscle Cells

et al. 2013

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Uterine leiomyomas (ULs) are benign tumors occurring in the majority of reproductive aged women. Despite the high prevalence of these tumors, little is known about their etiology. A hallmark of ULs is the excessive deposition of extracellular matrix (ECM), primarily collagens. Collagens are known to modulate cell behavior and function singularly or through interactions with integrins and growth factor-mediated mitogenic pathways. To better understand the pathogenesis of ULs and the role of ECM collagens in their growth, we investigated the interaction of leiomyoma smooth muscle cells (LSMCs) with two different forms of collagen, non-polymerized collagen (monomeric) and polymerized collagen (fibrillar), in the absence or presence of platelet-derived growth factor (PDGF), an abundant growth factor in ULs. Primary cultures of human LSMCS from symptomatic patients were grown on these two different collagen matrices and their morphology, cytoskeletal organization, cellular proliferation, and signaling pathways were evaluated. Our results showed that LSMCs had distinct morphologies on the different collagen matrices and their basal as well as PDGF-stimulated proliferation varied on these matrices. These differences in proliferation were accompanied by changes in cell cycle progression and p21, an inhibitory cell cycle protein. In addition we found alterations in the phosphorylation of focal adhesion kinase, cytoskeletal reorganization, and activation of the mitogen activated protein kinase (MAPK) signaling pathway. In conclusion, our results demonstrate a direct effect of ECM on the proliferation of LSMCs through interplay between the collagen matrix and the PDGF-stimulated MAPK pathway. In addition, these findings will pave the way for identifying novel therapeutic approaches for ULs that target ECM proteins and their signaling pathways in ULs.

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An essential role of p27 downregulation in fenvalerate-induced cell growth in human uterine leiomyoma and smooth muscle cells

Abstract: essential role of p27 downregulation in fenvalerate-induced cell growth in human uterine leiomyoma and smooth muscle cells.

Cited by 10 publications

References 29 publications

In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment

In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment

Aspirin inhibits the proliferation of human uterine leiomyoma cells by downregulation of K-Ras-p110α interaction

Extracellular Matrix Collagen Alters Cell Proliferation and Cell Cycle Progression of Human Uterine Leiomyoma Smooth Muscle Cells

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