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Full-Text Articles in Obstetrics and Gynecology
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium responds to unopposed estrogen stimulation with rapid cell proliferation. Progesterone protects the endometrium against the hyperplastic effects of estradiol (E2) through progesterone receptors (PRs), of which two isoforms are expressed: human (h) PRA and PRB. hPRB has a longer NH2 terminus and may function differently from hPRA. Thus, the relative expression of hPRA:hPRB is likely to be important for the action of progesterone. We hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer, leading to a lack of normal progesterone protection against the growth-promoting effects of E2. To test this hypothesis, well-differentiated Ishikawa endometrial cancer …
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Kimberly K. Leslie
Recent studies failed to detect estrogen receptors in primate follicles. This study was initiated to determine whether estrogen receptor (ER) messenger ribonucleic acid (mRNA) is present in human granulosa cells and, further, if functional ER proteins are present. To evaluate the presence of ER, RNA from human granulosa cells obtained at the time of oocyte retrieval for assisted reproduction was extracted, and complementary DNA synthesis was performed by the reverse transcriptase-polymerase chain reaction. Oligonucleotide primers were used to amplify basepairs 570-852 in the B- and C- domains of the ER mRNA. Southern blotting was performed and confirmed that the amplified …
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
Kimberly K. Leslie
Most of our knowledge of ovarian physiology is based upon studies that have demonstrated functional oestrogen receptors in the ovaries of lower animal species. The presence of oestrogen receptors in primate granulosa cells has been questioned by some investigators. However, we have found oestrogen receptor messenger RNA in human granulosa cells by reverse transcriptase-PCR assay. Furthermore, using immortalized granulosa cell lines transfected with a plasmid containing an oestrogen response element, a functional oestrogen receptor was confirmed. These experiments strongly support the hypothesis that human granulosa cells express biologically active oestrogen receptor.
Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin
Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin
Kimberly K. Leslie
OBJECTIVE: The antiestrogen tamoxifen has been found to be effective in decreasing glioblastoma cell proliferation, but the mechanism underlying this effect and whether it is through the estrogen receptor (ER) is controversial. The objective of this study was to determine whether ERs are present in three human glioblastoma cell lines--HS683, U138MG, and JHN J889H--using the most sensitive techniques available. METHODS: Ligand binding and flow cytometry were employed to identify estrogen and progesterone receptors. The reverse transcriptase-polymerase chain reaction was used to identify ER mRNA, and a novel reporter gene transfection assay demonstrated that the ER was capable of activating gene …
A Phase Ii Evaluation Of Lapatinib In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, A. Garcia, M. Sill, H. Lankes, A. Godwin, R. Mannel, D. Armstrong, R. Carolla, M. Liepman, N. Spirtos, E. Fischer, Kimberly Leslie
A Phase Ii Evaluation Of Lapatinib In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, A. Garcia, M. Sill, H. Lankes, A. Godwin, R. Mannel, D. Armstrong, R. Carolla, M. Liepman, N. Spirtos, E. Fischer, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations. METHODS: Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. …
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium and cancers derived from it are classic models of hormone action: estrogen promotes growth and progesterone inhibits proliferation and results in differentiation. We have now identified a major pathway through which progesterone causes these growth-limiting effects. Ligand-bound progesterone receptors modulate the composition and transcriptional activity of members of the activating protein-1 (AP-1) family, and in particular, c-Jun. First, a dominant negative form of c-Jun inhibits the constitutive growth of Hec50co cells in a manner similar to the effects of progesterone through progesterone B receptors. Second, progesterone inhibits the transcriptional activity of the AP-1 complex in reporter gene …