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Full-Text Articles in Medicine and Health Sciences
Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange
Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange
Kimberly K. Leslie
No abstract provided.
Molecular Tools To Reestablish Progestin Control Of Endometrial Cancer Cell Proliferation., D. Dai, N. Kumar, D. Wolf, Kimberly Leslie
Molecular Tools To Reestablish Progestin Control Of Endometrial Cancer Cell Proliferation., D. Dai, N. Kumar, D. Wolf, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Endometrial cancers often arise in a setting of estrogen stimulation unopposed by the differentiating effects of progesterone. Our laboratory and others have previously shown that progesterone receptor down-regulation or perturbation of progesterone receptor isoform A or B expression is associated with the development of poorly differentiated endometrial cancers that are not growth inhibited by progestins. The purpose of these studies was to reestablish high progesterone receptor isoform A and B gene expressions in such endometrial cancer cells and to examine the effects of progestin treatment on cell growth and metastatic potential after this transformation. STUDY DESIGN: To induce high …
Identification Of Proteins Within The Nuclear Factor-Kappa B Transcriptional Complex Including Estrogen Receptor-Alpha, I. Feldman, G. Feldman, C. Mobarak, J. Dunkelberg, Kimberly Leslie
Identification Of Proteins Within The Nuclear Factor-Kappa B Transcriptional Complex Including Estrogen Receptor-Alpha, I. Feldman, G. Feldman, C. Mobarak, J. Dunkelberg, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: The objective of the study was to determine whether cross-talk occurs between estrogen receptors (ERs) and nuclear factor-kappa-B (NF-kappaB), to assess the functional consequences of such an ER/NF-kappaB interaction, and to identify other unknown regulatory proteins that may participate in the NF-kappaB transcriptional complex. STUDY DESIGN: Electromobility gel shifts, reporter gene assays, and mass spectrometry were used to identify proteins interacting with the NF-kappaB deoxyribonucleic acid (DNA) response element. RESULTS: ER and the p65 subunit of NF-kappaB colocalized on DNA. This interaction was inhibitory for ER transcriptional activity. Sequencing of proteins bound to the NF-kappaB/DNA complex identified DNA-modifying enzymes, …
Gene Regulation Profiles By Progesterone And Dexamethasone In Human Endometrial Cancer Ishikawa H Cells, S. Davies, Donghai Dai, G. Pickett, Kimberly Leslie
Gene Regulation Profiles By Progesterone And Dexamethasone In Human Endometrial Cancer Ishikawa H Cells, S. Davies, Donghai Dai, G. Pickett, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Progesterone and glucocorticoids such as dexamethasone mediate distinct biological functions, yet they bind to receptors that recognize the same consensus DNA response element. In breast cancer, progestins are associated with the incidence and progression of tumors, whereas glucocorticoids are growth-suppressive in mammary cancer cells; the differential effects of these two steroids are less well understood in the hormone-dependent disease cancer of the uterine endometrium. We set out to identify genes that are regulated by progesterone through progesterone receptors and dexamethasone through glucocorticoid receptors in a well-differentiated human endometrial cancer cell line. METHODS: PR- and GR-positive Ishikawa H endometrial cancer …
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Nuclear factor kappa B (NFkappaB) is a strong anti-apoptotic factor, which is constitutively active in human endometrial cancer cells. Progesterone is the principal growth inhibitory hormone in the endometrial epithelium and promotes apoptosis. To identify the pathways through which progesterone controls NFkappaB function, we explored its genomic and non-genomic effects in endometrial cancer cells. METHODS: PR-negative Hec50co endometrial cancer cells were engineered to express high levels of the A or B isoform of PR (PRA or PRB) by adenoviral infection. Cells were treated with progesterone or vehicle alone, and RNA was isolated. Affymetrix microarrays were performed and transcriptional control …
Egfr Isoforms And Gene Regulation In Human Endometrial Cancer Cells, L. Albitar, G. Pickett, M. Morgan, J. Wilken, N. Maihle, Kimberly Leslie
Egfr Isoforms And Gene Regulation In Human Endometrial Cancer Cells, L. Albitar, G. Pickett, M. Morgan, J. Wilken, N. Maihle, Kimberly Leslie
Kimberly K. Leslie
BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) constitute a principal growth-promoting pathway in endometrial cancer cells. Pre-clinical studies were undertaken to compare the expression of EGFR isoforms and the downstream effects of activating or blocking EGFR function in Ishikawa H cells, derived from a moderately differentiated type I endometrioid adenocarcinoma, or in Hec50co cells, derived from a poorly differentiated type II adenocarcinoma with papillary serous sub-differentiation. RESULTS: We investigated whether EGFR mutations are present in the tyrosine kinase domain (exons 18-22) of EGFR and also whether EGFR isoforms are expressed in the Ishikawa H or Hec50co cell lines. …
Models Representing Type I And Type Ii Human Endometrial Cancers: Ishikawa H And Hec50co Cells, L. Albitar, G. Pickett, M. Morgan, S. Davies, Kimberly Leslie
Models Representing Type I And Type Ii Human Endometrial Cancers: Ishikawa H And Hec50co Cells, L. Albitar, G. Pickett, M. Morgan, S. Davies, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Endometrial cancer models are critical to the advancement of investigation, and Ishikawa H and Hec50co cells have been used as research tools. The purpose of these studies is to verify the degree to which these commonly used cell models share the molecular characteristics of the two major in vivo endometrial cancer subtypes, I and II. METHODS: The studies reported include an analysis of pathologic features, tumor suppressor mutations, detailed karyotyping, and cell cycle regulation. RESULTS: Ishikawa H cells are hormone responsive and have lost PTEN expression. In addition they have lost RB1 expression due to a deletion in exon …
Knockdown Of Mtdh Sensitizes Endometrial Cancer Cells To Cell Death Induction By Death Receptor Ligand Trail And Hdac Inhibitor Lbh589 Co-Treatment, Xiangbing Meng, Pavla Brachova, Shujie Yang, Zhi Xiong, Yuping Zhang, Khristina Thiel, Kimberly Leslie
Knockdown Of Mtdh Sensitizes Endometrial Cancer Cells To Cell Death Induction By Death Receptor Ligand Trail And Hdac Inhibitor Lbh589 Co-Treatment, Xiangbing Meng, Pavla Brachova, Shujie Yang, Zhi Xiong, Yuping Zhang, Khristina Thiel, Kimberly Leslie
Kimberly K. Leslie
Understanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH correlates with poor clinical outcome in breast cancer, neuroblastoma, hepatocellular carcinoma and prostate cancer. MTDH is also highly expressed in advanced endometrial cancers, a disease for which new therapies are urgently needed. In this present study, we focused on the therapeutic benefit of MTDH depletion in endometrial cancer cells to restore sensitivity to cell death. Cells were treated with a combination of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), which …