scholarly journals LASP-1 interacts with ErbB2 in ovarian cancer cells

2021 ◽  
Author(s):  
Chirukandath Sidhanth ◽  
Sadhanandhan Bindhya ◽  
Aboo Shabna ◽  
Shyama Krishnapriya ◽  
Pacharla Manasa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ductal Carcinoma ◽  
Direct Interaction ◽  
Surface Epithelium ◽  
Ovarian Cancer Cells ◽  
Spectrometric Analysis ◽  
Independent Dataset ◽  
Ovarian Cancer Cell Lines ◽  
Ovarian Tumours ◽  
Erbb2 Amplification

LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the  tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n=101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (p <0.001). Analysis of the expression of an independent dataset of ovarian and breast tumors from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (p<0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.

scholarly journals Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells

2006 ◽  
Vol 13 (2) ◽  
pp. 641-651 ◽  
Author(s):  
Jung-Hye Choi ◽  
Kyung-Chul Choi ◽  
Nelly Auersperg ◽  
Peter C K Leung
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Ovarian Cancer Cell ◽  
Ovarian Surface Epithelium ◽  
Gonadotropin Releasing Hormone ◽  
Surface Epithelium ◽  
Ovarian Cancer Cells ◽  
Mrna Levels ◽  
Ovarian Surface ◽  
Ovarian Cancer Cell Lines

Although gonadotropin-releasing hormone (GnRH) has been shown to play a role as an autocrine/ paracrine regulator of cell growth in ovarian surface epithelium and ovarian cancer, the factors which regulate the expression of GnRH and its receptor in these cells are not well characterized. In the present study, we employed real-time PCR to determine the potential regulatory effect of gonadotropins on the expression levels of GnRH I (the mammalian GnRH), GnRH II (a second form of GnRH) and their common receptor (GnRHR) in immortalized ovarian surface epithelial (IOSE-80 and IOSE-80PC) cells and ovarian cancer cell lines (A2780, BG-1, CaOV-3, OVCAR-3 and SKOV-3). The cells were treated with increasing concentrations (100 and 1000 ng/ml) of recombinant follicle-stimulating hormone (FSH) or luteinizing hormone (LH) for 24 h. Treatment with FSH or LH reduced GnRH II mRNA levels in both IOSE cell lines and in three out of five ovarian cancer cell lines (A2780, BG-1 and OVCAR-3). A significant decrease in GnRHR mRNA levels was observed in IOSE and ovarian cancer cells, except CaOV-3 cells, following treatment with FSH or LH. In contrast, treatment with either FSH or LH had no effect on GnRH I mRNA levels in these cells, suggesting that gonadotropins regulate the two forms of GnRH and its receptor differentially. In separate experiments, the effect of gonadotropins on the anti-proliferative action of GnRH I and GnRH II agonists in IOSE-80, OVCAR-3 and SKOV-3 cells was investigated. The cells were pretreated with FSH or LH (100 ng/ml) for 24 h after which they were treated with either GnRH I or GnRH II (100 ng/ml) for 2 days, and cell growth was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. Pretreatment of the cells with FSH or LH significantly reversed the growth inhibitory effect of GnRH I and GnRH II agonists in these cell types. These results provide the first demonstration of a potential interaction between gonadotropins and the GnRH system in the growth regulation of normal ovarian surface epithelium and its neoplastic counterparts.

scholarly journals miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Qin Zhang ◽  
Shuxiang Zhang
Keyword(s):  
Ovarian Cancer ◽  
Ionizing Radiation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tissues

Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN.

scholarly journals Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Li ◽  
Jie Yang ◽  
Ben Yang ◽  
Guoqing Zhao ◽  
Hai Lin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cell Biology ◽  
Ovarian Cancer Cell ◽  
Pain Treatment ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Growth ◽  
Ovarian Cancer Cell Lines ◽  
Rna Immunoprecipitation

Ketamine is widely used for cancer pain treatment in clinic, and has been shown to inhibit various tumor cells growth. However, the effect of ketamine on ovarian cancer cells growth and the downstream molecules has not been defined. In the present study, we found that ketamine significantly inhibited the proliferation and survival of six ovarian cancer cell lines. Moreover, ketamine induced ovarian cancer cell cycle arrest, apoptosis, and inhibited colony formation capacity. Since lncRNAs have been identified as key regulators of cancer development, we performed bioinformatics analysis of a GEO dataset and found fourteen significantly altered lncRNAs in ovarian cancer patients. We then investigated the effect of ketamine on these lncRNAs, and found that ketamine regulated the expression of lncRNA PVT1. Mechanistically, ketamine regulated P300-mediated H3K27 acetylation activation in the promoter of PVT1. Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. Our study revealed that ketamine could be a potential therapeutic strategy for ovarian cancer patients.

Ovarian Cancer Cell Invasiveness Correlates With Increased Cell Deformability

2012 ◽  
Author(s):  
Wenwei Xu ◽  
Roman Mezencev ◽  
Byungkyu Kim ◽  
Lijuan Wang ◽  
John McDonald ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Single Cells ◽  
Metastatic Cancer ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
Ovarian Cancer Cells ◽  
Cell Deformability ◽  
Ovarian Cells ◽  
And Migration

Cancer cells undergo a variety of biochemical and biophysical transformations when compared to identical cells displaying a healthy phenotypic state, cancer cells show a drastic reduction of stiffness upon malignancy[1, 2] and change of stiffness of single cells can indicate the presence of disease [3–6]. Besides, metastatic cancer has a higher deformability than their benign counterparts[7, 8]. Using atomic force microscopy, we demonstrated that cancerous ovarian cells (OVCAR3, OVCAR4, HEY and HEYA8) are substantially softer than the healthy immortalized ovarian surface epithelium (IOSE) cells. In addition, within the different types of cancerous ovarian cells, increased invasiveness and migration are directly correlated with increased cell deformability. These results indicate that stiffness of individual cells can distinguish not only ovarian cancer cells from healthy cells types, but also invasive cancer types from less invasive types. Stiffness may provide an alternative and convenient biomarker to grade the metastasis potential of cancer cells.

LncRNA SDHAP1 confers paclitaxel resistance of ovarian cancer by regulating EIF4G2 expression via miR-4465

2020 ◽  
Vol 168 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Hui Zhao ◽  
Aixia Wang ◽  
Zhiwei Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Regulatory Function ◽  
Ovarian Cancer Cells ◽  
Chemotherapeutic Resistance ◽  
Ovarian Cancer Cell Lines

Abstract Ovarian cancer has ranked as one of the leading causes of female morbidity and mortality around the world, which affects ∼239,000 patients and causes 152,000 deaths every year. Chemotherapeutic resistance of ovarian cancer remains a devastating actuality in clinic. The aberrant upregulation of long non-coding RNA succinate dehydrogenase complex flavoprotein subunit A pseudogene 1 (lncRNA SDHAP1) in the Paclitaxel (PTX)-resistant ovarian cancer cell lines has been reported. However, studies focussed on SDHAP1 in its regulatory function of chemotherapeutic resistance in ovarian cancer are limited, and the detailed mechanisms remain unclear. In this study, we demonstrated that SDHAP1 was upregulated in PTX-resistant SKOV3 and Hey-8 ovarian cancer cell lines while the level of miR-4465 was downregulated. Knocking-down SDHAP1 induced re-acquirement of chemo-sensitivity to PTX in ovarian cancer cells in vitro. Mechanically, SDHAP1 upregulated the expression of EIF4G2 by sponging miR-4465 and thus facilitated the PTX-induced apoptosis in ovarian cancer cells. The regulation network involving SDHAP1, miR-4465 and EIF4G2 could be a potential therapy target for the PTX-resistant ovarian cancer.

scholarly journals Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769430 ◽  
Author(s):  
Zhenhua Du ◽  
Xianqun Sha
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Natural Form ◽  
Ovarian Cancer Cell Lines ◽  
Induced Apoptosis ◽  
Tumor Suppressive Function ◽  
Cancer Tissues

Curcumin is a natural agent that has ability to dampen tumor cells’ growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells’ malignant progress via up-regulating miR-551a.

scholarly journals Follicle-Stimulating Hormone Is an Autocrine Regulator of the Ovarian Cancer Metastatic Niche Through Notch Signaling

2018 ◽  
Vol 3 (2) ◽  
pp. 340-357 ◽  
Author(s):  
Sakshi Gera ◽  
Sandeep Kumar S. ◽  
Shalini N Swamy ◽  
Rahul Bhagat ◽  
Annapurna Vadaparty ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Fsh Receptor ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Tissues

Abstract The association between the upregulated Notch and FSH signaling and ovarian cancer is well documented. However, their signaling has been investigated independently and only in the primary tumor tissues. The aim of this study was to investigate the interactive effects of FSH and Notch signaling on ovarian cancer proliferation, formation, and maintenance of disseminated ovarian cancer cells. The roles of Notch and FSH in ovarian cancer pathogenesis were investigated with ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR). FSH upregulated Notch signaling and proliferation in ovarian cancer cells. High levels of FSH were detected in the ascites of patients with serous ovarian adenocarcinoma. Spheroids from the patients’ ascites, as well as the spheroids from ovarian cancer cell lines under low attachment culture conditions, expressed FSHβ subunit mRNA and secreted the hormone into the medium. In contrast, primary ovarian tumor tissues and cell line monolayers expressed very low levels of FSHβ. Ovarian cancer cell spheroids also exhibited higher expression of FSH receptor and Notch downstream genes than their monolayer counterparts. A combination of FSHR and Notch antagonistic antibodies significantly inhibited spheroid formation and cell proliferation in vitro. This study demonstrates that spheroids in ascites express and secrete FSH, which regulates cancer cell proliferation and spheroidogenesis through Notch signaling, suggesting that FSH is an autocrine regulator of cancer metastasis. Furthermore, Notch and FSHR are potential immunotherapeutic targets for ovarian cancer treatment.

Mechanism of Cepharanthine Cytotoxicity in Human Ovarian Cancer Cells

Planta Medica ◽  
2018 ◽  
Vol 85 (01) ◽  
pp. 41-47 ◽  
Author(s):  
Vilawan Payon ◽  
Chanaporn Kongsaden ◽  
Wannarasmi Ketchart ◽  
Apiwat Mutirangura ◽  
Piyanuch Wonganan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cell ◽  
Apoptotic Cell ◽  
Chemotherapeutic Agents ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ovarian Cancer Cell Lines ◽  
Underlying Mechanisms

AbstractCepharanthine (CEP), a medicinal product derived from Stephania cephalantha Hayata, possesses a potent cytotoxicity against several types of cancers. Recently, we have found that CEP could efficiently inhibit the growth of mutated p53 colon cancer cells, which are often resistant to commonly used chemotherapeutic agents. In this study, we evaluated the cytotoxic effect and the underlying mechanisms of CEP on both chemosensitive CaOV-3 and chemoresistant OVCAR-3 ovarian cancer cell lines. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a time- and concentration-dependent manner. CEP arrested CaOV-3 and OVCAR-3 cells in the G1 phase and S phase of cell cycle, respectively. Western blot analysis demonstrated that CEP markedly increased the expression of p21Waf1 protein and decreased the expression of cyclins A and D proteins in both CaOV-3 and OVCAR-3 cells. Additionally, CEP triggered apoptotic cell death in OVCAR-3 cells. Taken together, the above results suggest that CEP is a promising anticancer drug for ovarian cancer.

Defining the mechanisms by which leptin stimulates proliferation of ovarian cancer cells

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15017-15017
Author(s):  
A. B. Olawaiye ◽  
H. Sakamoto ◽  
T. Serikawa ◽  
A. Friel ◽  
R. Kiyama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Sufficient Evidence ◽  
Surface Epithelium ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ovarian Cancer Cells ◽  
Ovarian Surface ◽  
Potential Biomarker ◽  
Ovca Cell

15017 Background: Ovarian cancer (OvCa) ranks fourth as the cause of death related to cancer in women in the U.S. The vast majority (>90%) of OvCa originates from the ovarian surface epithelium. There is sufficient evidence to suggest that hormones, especially estrogen, may be involved in the etiopathogenesis of epithelial OvCa. Recent studies indicate that leptin participates either directly or indirectly to promote carcinogenesis in both breast and endometrial cancers. Furthermore it has been proposed that leptin may elicit its action via an estrogen related pathway. Leptin can stimulate proliferation of some OvCa cell lines and has been implicated as a potential biomarker for OvCa. However the mechanism(s) by which leptin contributes to the growth of OvCa has yet to be defined. We hypothesize that leptin’s effect will be mediated in part by estrogen receptor (ER) pathways. Methods: Three epithelial OvCa cell lines (IGROV1, OVCAR5 and TOV21G) and one benign human ovarian surface epithelial cell line (HOSE) were evaluated. Enzyme linked immunosorbent assay (ELISA) and Western blotting were used to assess leptin and leptin receptor (ObR), respectively. Leptin (0.06 nM–6.25 nM) induced effects on cell proliferation were assessed in the presence or absence of an aromatase enzyme inhibitor (Anastrozole) or the ER antagonist (ICI182780). Further, we explored leptin-induced effects on ERα promoter activity as evidenced by change in fluorescence via a dual luciferase promoter reporter. All experiments were conducted in triplicate. All data were subjected to ANOVA followed by Tukey’s post hoc test (p < 0.05). Results: All ovarian cell lines expressed ObR; whereas, no measurable amounts of leptin were detected in conditioned media. Leptin stimulated cell proliferation in both the benign and malignant lines. Leptin-induced cell proliferation was inhibited by Anastrozole and ICI182780. Furthermore, leptin stimulated luciferase activity of the ERα promoter/reporter. Conclusions: Leptin promotes proliferation of benign and malignant ovarian epithelial cells and appears to be mediated, at least in part, via aromatase and ER which may have therapeutic implications. This work was supported by the Vincent Memorial Hospital, SG Komen Foundation and the Advanced Medical Research Foundation. No significant financial relationships to disclose.

scholarly journals LHRH might act as a negative autocrine regulator of proliferation of human ovarian cancer

2000 ◽  
pp. 665-670 ◽  
Author(s):  
G Emons ◽  
S Weiss ◽  
O Ortmann ◽  
C Grundker ◽  
KD Schulz
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Lhrh Agonists ◽  
Ovarian Cancer Cell Lines ◽  
Low Concentrations

OBJECTIVE: More than 80% of human ovarian cancers express LHRH and its receptor. The proliferation of human ovarian cancer cell lines is reduced by both LHRH agonists and antagonists. This study was designed to further clarify the possible biological function of this LHRH system. DESIGN: As LHRH agonists and antagonists uniformly reduce proliferation of human ovarian cancer in a dose-dependent way, the effect of low concentrations of authentic LHRH was studied. In addition, longer periods of treatment (up to 9 days) were analyzed. To assess the physiological role of LHRH produced by ovarian cancer cells it was neutralized by adequate concentrations of a specific LHRH antiserum. METHODS: Human ovarian cancer cells EFO-21 and EFO-27, which express LHRH and its receptor, were incubated for 1-9 days with increasing concentrations (1pmol/l to 10 micromol/l) of authentic LHRH or with concentrations of LHRH antiserum capable of neutralizing at least 1nmol/l LHRH. Proliferation was assessed by counting cells. RESULTS AND CONCLUSIONS: Authentic LHRH reduced time- and dose-dependently proliferation (by maximally mean+/-s.e.m. 32.7 +/- 4.4%, Newman-Keuls, P < 0.001) of both ovarian cancer cell lines. At very low concentrations (1pmol/l) a marginal reduction of proliferation or no effect was observed. A mitogenic effect of authentic LHRH was never detected. Treatment of ovarian cancer cell cultures with antiserum to LHRH significantly increased (up to mean+/-s.e.m. 121.0 +/- 2.8% of controls, Newman-Keuls P <0.001) proliferation of EFO-21 and EFO-27 cells. These findings suggest that LHRH produced by human ovarian cancer cells might act as a negative autocrine regulator of proliferation.

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