Increased Expression of Dachshund Homolog 1 in Ovarian Cancer as a Predictor for Poor Outcome

2012 ◽  
Vol 22 (3) ◽  
pp. 386-393 ◽  
Author(s):  
Fei Liang ◽  
Qingtao Lü ◽  
Shuyu Sun ◽  
Jie Zhou ◽  
Vladimir M. Popov ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Immunohistochemical Staining ◽  
Normal Tissue ◽  
Prognostic Value ◽  
Functional Relationship ◽  
Estrogen Receptor Α ◽  
Cancer Growth ◽  
Protein Levels

ObjectiveThis study aimed to determine the functional relationship between the levels of dachshund homolog 1 (DACH1) expression and different subtypes of ovarian cancer and to investigate the possible prognostic value of DACH1 in ovarian cancer.MethodsImmunohistochemical staining was deployed to determine the protein levels of DACH1. Staining was performed on patient samples, for whom the detailed follow-up data have been acquired during the last 10 years. Normal, benign, borderline, cancer, and metastatic ovarian cancer samples were included in this study.ResultsThe results of our study show that DACH1 protein levels increase with the invasiveness of the ovarian cancer. As the cancer progresses from benign and borderline to metastatic, DACH1 protein expression increases as well. Moreover, with the increase in expression, the subcellular distribution of DACH1 changes from nucleus in normal tissue to cytoplasm in cancer. Finally, DACH1 expression levels were compared with estrogen receptor α (ERα) levels, and the results showed that overall DACH1 levels were higher, whereas also DACH1 exhibited increased cytoplasmic expression in ERα-positive ovarian cancer samples.ConclusionsThese results indicate that DACH1 is highly expressed in metastatic ovarian cancer compared with that of normal, benign, and borderline ovarian tissues and that it could play an important role in cancer growth.

scholarly journals PARP7 and Mono-ADP-Ribosylation Negatively Regulate Estrogen Receptor α Signaling in Human Breast Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 623
Author(s):  
Marit Rasmussen ◽  
Susanna Tan ◽  
Venkata S. Somisetty ◽  
David Hutin ◽  
Ninni Elise Olafsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Protein Modification ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
Transactivation Domain ◽  
Adp Ribosylation ◽  
Protein Levels ◽  
17Β Estradiol ◽  
Mcf 7

ADP-ribosylation is a post-translational protein modification catalyzed by a family of proteins known as poly-ADP-ribose polymerases. PARP7 (TIPARP; ARTD14) is a mono-ADP-ribosyltransferase involved in several cellular processes, including responses to hypoxia, innate immunity and regulation of nuclear receptors. Since previous studies suggested that PARP7 was regulated by 17β-estradiol, we investigated whether PARP7 regulates estrogen receptor α signaling. We confirmed the 17β-estradiol-dependent increases of PARP7 mRNA and protein levels in MCF-7 cells, and observed recruitment of estrogen receptor α to the promoter of PARP7. Overexpression of PARP7 decreased ligand-dependent estrogen receptor α signaling, while treatment of PARP7 knockout MCF-7 cells with 17β-estradiol resulted in increased expression of and recruitment to estrogen receptor α target genes, in addition to increased proliferation. Co-immunoprecipitation assays revealed that PARP7 mono-ADP-ribosylated estrogen receptor α, and mass spectrometry mapped the modified peptides to the receptor’s ligand-independent transactivation domain. Co-immunoprecipitation with truncated estrogen receptor α variants identified that the hinge region of the receptor is required for PARP7-dependent mono-ADP-ribosylation. These results imply that PARP7-mediated mono-ADP-ribosylation may play an important role in estrogen receptor positive breast cancer.

Selected Contribution: Estrogen receptor-α antisense decreases brain estrogen receptor levels and affects ventilation in male and female rats

2001 ◽  
Vol 91 (4) ◽  
pp. 1886-1892 ◽  
Author(s):  
Shashita R. Inamdar ◽  
Kathleen M. Eyster ◽  
Evelyn H. Schlenker
Keyword(s):  
Estrogen Receptor ◽  
Aspartic Acid ◽  
Estrogen Receptor Α ◽  
Neonatal Rat ◽  
Female Rats ◽  
Antisense Oligodeoxynucleotide ◽  
Protein Levels ◽  
Ventilatory Responses ◽  
Rat Pups ◽  
Male And Female Rats

We hypothesized that administration of an antisense oligodeoxynucleotide (ODN) to estrogen receptor (ER)-α mRNA decreases the ER protein in the neonatal rat brain, alters the sex-specific ventilatory responses to aspartic acid in rats, and counteracts the effects of testosterone proportionate (TP) in females. One-day-old rat pups were injected intraventricularly with vehicle, antisense ER ODN, or scrambled ODN control. Additional groups of females received TP or vehicle and one of the three treatments. Brain ER protein levels were decreased by 65% at 6 h and 35% at 24 h after antisense ODN. Aspartic acid decreased ventilation in all groups of weanling males and females except ER ODN-treated females and TP-vehicle-treated females. Aspartic acid decreased ventilation in all groups of adult females except those given TP and in males. Weanling ER ODN-treated rats were shorter and weighed less than controls. Only adult ER ODN-treated males exhibited these traits. Thus neonatal ER affects aspartic acid modulation of breathing and body growth in a sex-specific and developmental manner.

scholarly journals Foxl2, a Forkhead Transcription Factor, Modulates Nonclassical Activity of the Estrogen Receptor-α

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5085-5093 ◽  
Author(s):  
So-Youn Kim ◽  
Jeffrey Weiss ◽  
Minghan Tong ◽  
Monica M. Laronda ◽  
Eun-Jig Lee ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Transcription Factor ◽  
Direct Action ◽  
Ovarian Follicle ◽  
Estrogen Receptor Α ◽  
Ovary Development ◽  
Activator Protein 1 ◽  
Forkhead Transcription Factor ◽  
Protein Levels ◽  
And Function

Foxl2 is a forkhead transcription factor required for ovary development and ovarian follicle maturation. In this report, we identified and characterized a functional relationship between Foxl2 expression and estrogen receptor (ER)-α signaling. We show that Foxl2 has no effect on classical ERα-mediated transcription, which occurs through canonical estrogen response elements. However, Foxl2 suppresses ERα signaling through nonclassical tethered transcriptional pathways. Specifically, the selective ER modulator tamoxifen stimulates activator protein-1 (AP1)-dependent transcription via the ERα, and this enhancement is blocked by Foxl2. Two lines of evidence suggest that Foxl2 suppression is mediated by physical interactions with ERα rather than direct action at AP1 binding sites. First, ERα is coimmunoprecipitated with Foxl2. Second, activation of a upstream activating sequence (UAS) reporter by Gal4-cJun in the presence of ERα and tamoxifen was blocked by Foxl2, demonstrating suppression in the absence of an AP1 site. Cyclooxygenase-2 (COX2), which is required for ovulation, was identified through expression profiling as a candidate physiological target for nonclassical ERα signaling and thus modulation by ERα/Foxl2 interactions. This possibility was confirmed by two sets of experiments. COX2 protein levels were induced by ERα in the presence of tamoxifen, and protein expression was suppressed by Foxl2. In addition, ERα stimulation of the COX2 promoter was repressed by Foxl2. We conclude that ERα and Foxl2 interact and that Foxl2 selectively suppresses ERα-mediated transcription of AP1-regulated genes. These data provide a potential point of convergence for ERα and Foxl2 to regulate ovarian development and function.

scholarly journals Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

2009 ◽  
Vol 202 (1) ◽  
pp. 167-177 ◽  
Author(s):  
Liyuan Tian ◽  
Zhiqiang Wu ◽  
Yali Zhao ◽  
Yuanguang Meng ◽  
Yiling Si ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Estrogen Receptor Α ◽  
Ovarian Cancer Cells ◽  
Induction Effect ◽  
Skov3 Cell ◽  
Signaling Transduction ◽  
Estrogen Response ◽  
Skov3 Cells

Previously, we investigated the induction effect of LRP16 expression by estrogen (17β-estradiol, E2) and established a feed-forward mechanism that activated estrogen receptor α (ERα) transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ERα signaling transduction by functioning as an ERα coactivator. In this study, we demonstrated that LRP16 expression was upregulated in E2-responsive BG-1 ovarian cancer cells, but was downregulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The unliganded ERα upregulated LRP16 expression and enhanced LRP16 promoter activity in SKOV3 cells; however, this induction was blocked by estrogen stimulation. Results from chromatin immunoprecipitation experiment revealed a strong recruitment of the unliganded ERα at LRP16 promoter in the absence of estrogen; however, ERα was largely released from the DNA upon E2 stimulation. Modulation in LRP16 expression level did not significantly change the proliferation rate of SKOV3 cells and the growth responsiveness of cells to E2. Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated estrogen response element-dependent ERα reporter gene activity and E2-induced c-Myc expression. Our study suggests a novel mechanism of estrogen resistance of ovarian cancer by which estrogen-repressed signaling pathway antagonizes estrogen-activated signaling transduction.

Immunohistologic Detection of Estrogen Receptor Alpha in Canine Mammary Tumors: Clinical and Pathologic Associations and Prognostic Significance

2000 ◽  
Vol 37 (3) ◽  
pp. 239-247 ◽  
Author(s):  
A. Nieto ◽  
L. Peña ◽  
M. D. Pérez-Alenza ◽  
M. A. Sánchez ◽  
J. M. Flores ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Lymph Node ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Mammary Tumors ◽  
Proliferation Index ◽  
Lymph Node Status ◽  
Canine Mammary Tumors

Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-α) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3–4 months. ER-α expression was higher in tumors of genitally intact and young bitches ( P < 0.01, P < 0.01) and in animals with regular estrous periods ( P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-α ( P = 0.04). Immunoexpression of ER-α decreased significantly with tumor size ( P = 0.05) and skin ulceration ( P = 0.01). Low levels of ER-α were significantly associated with lymph node involvement ( P < 0.01). Malignant tumors had lower ER-α expression than did benign tumors ( P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-α scores ( P = 0.05) in all tumors. Low ER-α levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up ( P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-α value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-α index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-α in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy.

Neonatal Experiences Differentially Influence Mammary Gland Morphology, Estrogen Receptor α Protein Levels, and Carcinogenesis in BALB/c Mice

2010 ◽  
Vol 3 (11) ◽  
pp. 1398-1408 ◽  
Author(s):  
Allison L. Boyd ◽  
Ayesha Salleh ◽  
Brent Humber ◽  
Janet Yee ◽  
Ladislav Tomes ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Estrogen Receptor Α ◽  
Protein Levels ◽  
Mammary Gland Morphology

scholarly journals Еstrogen receptor α (ESR1) and SRC family kinase (LYN) gene's mutations associated with ovarian cancer endocrine therapy resistance

2021 ◽  
Vol 8 (1) ◽  
pp. 10-16
Author(s):  
E. A. Shestakova
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Therapy Resistance ◽  
Estrogen Receptor Α ◽  
Endocrine Therapy Resistance ◽  
Lyn Kinase ◽  
Esr1 Gene ◽  
Gene Coding ◽  
Pubmed Database

Recently multiple data accumulated concerning mutations in the ESR1 gene coding estrogen receptor α (mutESR1) and in the LYN gene coding non receptor tyrosine kinase SRC family member (mutLYN) that are associated with endocrine therapy resistance and that could be considered as markers of endocrine therapy efficiency. In case of gynecologic cancers including ovarian cancer the most frequent mutESR1 are ESR1L536H/P/R/V , ESR1Y537S/N/C/H, ESR1D538G that emerge in the course of hormonotherapy especially using aromatase inhibitors. mutLYN including LYNE159K, LYND189Y, LYNK209N, LYNA370T, LYNG418R, LYNA503D are also identified. mutESR1 and mutLYN increase transcriptional activity of estrogen receptor α (ERα) coded with ESR1 gene and catalytic activity of LYN kinase inducing endocrine therapy resistance. Interdependence of ESR1 and LYN genes is revealed at the level of proteins that they code as the kinases of the SRC family including LYN activate ERα-dependent transcription due to the phosphorylation of ERα at Y537 amino-acid residue that is the most frequently mutated in tumors with endocrine therapy resistance. The aim of the review is revealing the clinical correlations of mutESR1 and mutLYN with the ovarian cancer endocrine therapy resistance that opens perspectives of mutESR1 and mutLYN use as new predictive markers of ovarian cancer and development of more efficient anti-tumor medicaments. In the review the information obtained from PubMed database for the last 20 years using the following key words: ESR1, LYN, mutation(s), estrogen receptor α (ERα), LYN kinase, SRC family kinases, ovarian cancer, gynecologic(al) cancer is discussed.

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