Effect of estradiol, progesterone and testosterone on apoptosis- and proliferation-induced MAPK signaling in human umbilical vein endothelial cells

Powazniak,

doi:10.3892/mmr_00000119

Cited by 12 publications

(16 citation statements)

References 26 publications

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“…As the ovarian cancer cells tested lack PR, the authors suggest P4 is functioning through MPRs. Treatment of human umbilical vein endothelial cells with supraphysiological levels of P4 was able to induce JNK phosphorylation, but JNK activation was not evident at physiological concentrations (Powazniak, Kempfer, de la Paz Dominguez et al, 2009). Studies evaluating P4 effects on epidermal growth factor (EGF) signaling in breast cancer cells revealed treatment of T47D-YB cells with R5020, a P4 agonist, for 48 h prior to EGF treatment resulted in JNK phosphorylation (Lange, Richer, Shen et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Progestin-mediated activation of MAPK and AKT in nuclear progesterone receptor negative breast epithelial cells: The role of membrane progesterone receptors

Salazar

Lerma-Ortiz

Hooks

et al. 2016

Gene

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Progesterone (P4), a steroid produced during estrous cycles and gestation for maintenance of pregnancy, also plays key roles in breast development to allow lactation post-parturition. Progestins (P4 and related steroids) are also implicated in breast cancer etiology. Hormone replacement therapy containing both estrogen and progestins increases breast cancer incidence while estrogen hormone therapy lowers breast cancer risk. P4 signaling via nuclear P4 receptors (PRs) has been extensively studied in breast cancer, however, progestin signaling via non-classical membrane bound progestin receptors (MPRs and PGRMC1) remains unclear. Moreover, P4 metabolites and synthetic progestins may bind membrane progestin receptors. We hypothesized that PR-negative breast epithelial cells express non-classical progestin receptors, which activate intracellular signaling pathways differently depending on nature of progestin. Therefore, our objectives for the current study were to determine expression of MPRs and PGRMC1 in two PR-negative non-tumorigenic breast epithelial cell lines, assess progestin-mediated signaling and biological functions. We determined five MPR isoforms and PGRMC1 were present in MCF10A cells and all progestin receptors but MPRβ in MCF12A cells. MCF10A and MCF12A cells were treated with P4, select P4 metabolites (5αP and 3αHP), medroxyprogesterone acetate (MPA), or a specific MPRAgonist (MPR-Ag) and phosphorylation of ERK, p38, JNK, and AKT was characterized following treatment. To our knowledge this is the first report of ERK and JNK activation in MCF10A and MCF12A cells with P4, P4 metabolites, MPA, and MPR-Ag. Activation of ERK and JNK in cells treated with MPR-Ag implicates MPRs may serve as the receptors responsible for their activation. In contrast, p38 activation varied with cell type and with progestin treatment. P4 and MPA promoted AKT phosphorylation in the MCF12A cell line only whereas no activation was observed in MCF10A cells. Interestingly, cellular proliferation increased in MCF10A cells treated with MPA or 5αP, while MPR-Ag tended to slightly decrease proliferation. Collectively, our data highlights the importance of investigating the effects of synthetic progestins in breast cancer biology. Our results add to the understanding that various progestins have on breast epithelial cells and underscores the importance of considering both membrane bound receptors and progestin type in breast cancer development.

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Section: Discussionmentioning

confidence: 99%

Progestin-mediated activation of MAPK and AKT in nuclear progesterone receptor negative breast epithelial cells: The role of membrane progesterone receptors

Salazar

Lerma-Ortiz

Hooks

et al. 2016

Gene

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“…The present study examined the possible mechanism underlying the action of periostin in endothelial cells. Previous studies revealed that growth factors stimulate angiogenesis via activating kinase signaling pathways, including PI3K/AKT, ERK1/2, FAK and p38/MAPK, to regulate endothelial cell migration, survival and vascular permeability ( 28 , 29 ). In the present study, periostin promoted HUVEC migration and tube formation by activating the ERK1/2 and FAK pathways.…”

Section: Discussionmentioning

confidence: 99%

Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin-1

Zhang

Nie

Chen

et al. 2014

Molecular Medicine Reports

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Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from keloid fibroblasts (KFs) promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and this effect may have been abrogated by the short hairpin RNA knockdown of periostin. Treatment with recombinant human periostin promoted the migration and tube formation of HUVECs by activating the extracellular signal-regulated kinase 1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased the secretion of vascular endothelial growth factor and angiopoietin-1 in the KFs. In conclusion, these data suggested that upregulation in the level of periostin may promote angiogenesis directly and indirectly in keloids and may be a key factor in keloid development. Periostin may, therefore, be a promising therapeutic target in the treatment of keloids and other angioproliferative diseases.

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“…Rat CMECs cultured for 48 h in hormone-free medium were plated at ~90% confluent in 24-well culture plates. After 12 h, the cell monolayer was scraped with a 1-ml pipette tip to create a cell-free zone [ 6 ]. The medium and dislodged cells were then aspirated, and the plates were rinsed with PBS.…”

Section: Methodsmentioning

confidence: 99%

“…Powazniak et al demonstrated that estradiol enhanced human umbilical vein endothelial cell activity (non-endometrial endothelial cells) in vitro and in vivo [ 6 ]. These cells play an important role in neovascularization, suggesting a promoting influence of estrogen on angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

17β-Estradiol Promotes Angiogenesis of Rat Cardiac Microvascular Endothelial Cells In Vitro

et al. 2018

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BackgroundThe formation of new blood vessels, known as angiogenesis, is critical for recovery from ischemic heart disease, and estrogen is considered an important factor in this process. Here, we investigated the effects of 17β-estradiol (17β-E2) on proliferation and migration of cardiac microvascular endothelial cells (CMECs) in vitro.Material/MethodsRat CMECs were isolated and cultured with 17β-E2 (0.001–1 μmol/l) in the absence or presence of the estrogen antagonist tamoxifen. Then, the expression level of estrogen receptor alpha was evaluated by using immunofluorescence assay, RT-PCR, and Western blot. Cell proliferation was detected by methyl thiazolyl tetrazolium analysis and the cell migration was verified by a scraping assay and quantified by a Transwell chamber assay. CMEC differentiation was examined using a tube formation assay. Vascular endothelial growth factor (VEGF) secretion was detected by enzyme-linked immunosorbent assay.ResultsCMECs exhibited homogenous, polygonal, exhibited contact inhibition, and had characteristically ovoid nuclei with 1 or 2 nucleoli, and the cytoplasm exhibited red fluorescence after staining for von Willebrand factor. 17β-E2 treatment upregulated estrogen receptor alpha expression in CMECs. 17β-E2 treatment significantly promoted the proliferation, migration, tubular structure formation, and VEGF secretion in CMECs. The maximal proliferation occurred in the presence of 0.01 μmol/l 17β-E2. Furthermore, estrogen and VEGF were found to synergistically stimulate angiogenesis.ConclusionsOur data show that 17β-E2 promotes angiogenesis in vitro and suggests that estrogen treatment as a novel therapeutic modality in the management of arterial insufficiency.

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Effect of estradiol, progesterone and testosterone on apoptosis- and proliferation-induced MAPK signaling in human umbilical vein endothelial cells

Cited by 12 publications

References 26 publications

Progestin-mediated activation of MAPK and AKT in nuclear progesterone receptor negative breast epithelial cells: The role of membrane progesterone receptors

Progestin-mediated activation of MAPK and AKT in nuclear progesterone receptor negative breast epithelial cells: The role of membrane progesterone receptors

Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin-1

17β-Estradiol Promotes Angiogenesis of Rat Cardiac Microvascular Endothelial Cells In Vitro

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