Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE150477 | GEO | 2020/05/14
REPOSITORIES: GEO
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Project description:Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells
| PRJNA632540 | ENA
Project description:The hormone prolactin is implicated in the pathogenesis of breast cancer, and a subset of prolactin-induced gene expression is mediated by HDAC6 activity. The NSAID, bufexamac, is a fairly specific inhibitor of HDAC6 and HDAC10. We used bufexamac in combination with prolactin treatment in MCF7 cells to determine differential expression under these conditions.
2016-05-07 | GSE81217 | GEO
Project description:The hormone prolactin is implicated in the pathogenesis of breast cancer, and a subset of prolactin-induced gene expression is mediated by CypA activity. The non-immunosuppressive prolyl isomerase inhibitor, NIM811, is an inhibitor of CypA. We used NIM811 in combination with prolactin treatment in T47D cells to determine differential expression under these conditions.
2020-06-03 | GSE151635 | GEO
Project description:The hormone, prolactin, has been implicated in breast cancer pathogenesis and regulates chromatin engagement by the transcription factor, STAT5A. STAT5A is known to inducibly bind promoters and cis-regulatory elements genome wide, though the mechanisms by which it exerts specificity and regulation of target gene expression remain enigmatic. We previously identified HDAC6 and HMGN2 as cofactors that facilitate prolactin induced, STAT5A mediated gene expression. Here, multi-condition STAT5A, HDAC6, and HMGN2 ChIP-seq with parallel condition RNA-seq are utilized to reveal the cis-regulatory landscape and cofactor dynamics underlying prolactin stimulated gene expression in breast cancer. We find that prolactin regulated genes are significantly enriched for cis-regulatory elements bound by HDAC6 and HMGN2, and that inducible STAT5A binding at enhancers, rather than promoters, conveys specificity for prolactin regulated genes. The selective HDAC6 inhibitor, ACY-241, blocks prolactin induced STAT5A chromatin engagement at cis-regulatory elements as well as a significant proportion of prolactin stimulated gene expression. We identify functional pathways known to contribute to the development and/or progression of breast cancer that are activated by prolactin and inhibited by ACY-241. Additionally, we find that the DNA sequences underlying shared STAT5A and HDAC6 binding-sites at enhancers are differentially enriched for estrogen response elements (ESR1 and ESR2 motifs) relative to enhancers bound by STAT5A alone. Gene set enrichment analysis identifies significant overlap of ERα regulated genes with genes regulated by prolactin, particularly prolactin regulated genes with promoters or enhancers co-occupied by both STAT5A and HDAC6.
2021-01-26 | GSE165452 | GEO
Project description:Most breast cancers are luminal, depending on estrogens for growth. The remainder lack estrogen receptors, are hormone-resistant and basal-like. It is thought that breast cancers arise from self-renewing normal stem cells that have undergone malignant transformation. However currently reported cancer stem cells are hormone insensitive and generate basal, rather than luminal tumors. We now describe true luminal hormone-responsive breast cancer stem cells that express estrogen and progesterone receptors. Their self-renewal capacity is protected by progesterone. Stem cell levels are depleted by estrogens as tumors transition into differentiated and homogeneous luminal states. But, if added to estrogens, progesterone promotes heterogeneity and “rescues” the stem cells. By keeping luminal cancer stem cells “safe”, progesterone, widely used for contraception and hormone replacement, could be harmful to breast cancer survivors or women with occult disease.
2016-01-31 | GSE65407 | GEO
Project description:We examined the global gene expression pattern of T cells regulated by progesterone to gain further insights into the regulatory mechanisms of progesterone. We found 325-347 cord blood T cell genes up or down-regulated by P4 in the presence or absence of exogenous TGFb1. Peripheral blood T cells were relatively unresponsive with only 30-70 genes regulated by P4. IL-6 receptor (IL-6R) expression was greatly down-regulated by progesterone in cord blood, but not PB, T cells. Overall, these differences in gene expression are consistent with the differential responses of cord blood and peripheral blood T cells to progesterone. To gain insights into the differences of progesterone and control dendritic cells, we performed a microarray study and found ~180 genes regulated by progesterone in dendritic cells. The gene expression information suggests that progesterone has the potential to alter dendritic cell responses to cytokines, chemokine production, and migration which in combination would control T cell differentiation.
2012-03-02 | GSE22025 | GEO
Project description:We examined the global gene expression pattern of T cells regulated by progesterone to gain further insights into the regulatory mechanisms of progesterone. We found 325-347 cord blood T cell genes up or down-regulated by P4 in the presence or absence of exogenous TGFb1. Peripheral blood T cells were relatively unresponsive with only 30-70 genes regulated by P4. IL-6 receptor (IL-6R) expression was greatly down-regulated by progesterone in cord blood, but not PB, T cells. Overall, these differences in gene expression are consistent with the differential responses of cord blood and peripheral blood T cells to progesterone. To gain insights into the differences of progesterone and control dendritic cells, we performed a microarray study and found ~180 genes regulated by progesterone in dendritic cells. The gene expression information suggests that progesterone has the potential to alter dendritic cell responses to cytokines, chemokine production, and migration which in combination would control T cell differentiation.
2012-03-02 | GSE22025 | GEO
Project description:Primary hyperparathyroidism is a common endocrine disorder frequently affecting postmenopausal women. In this study we have investigated expression of the prolactin receptor (PRLr) in a panel of 37 sporadic parathyroid tumours, as well as functionality in vitro in cultured parathyroid tumour cells. High levels of the prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues as compared to other reference tissues and breast cancer cells. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours PRLr immunoreactivity was observed in cytoplasm in all cases and in addition in the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim PRLr was expressed in cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells prolactin stimulation was associated with transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signaling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumors was significantly inversely correlated with plasma total Ca2+ levels. In conclusion, the prolactin receptor was found highly abundant in human parathyroid gland, parathyroid tumours, correlated with patient Ca2+ levels and functionally responsive to physiological levels of prolactin. These findings suggest a role for the prolactin receptor in human parathyroid adenomas. Expression profiling was done in parathyroid adenomas subjected to prolactin treatment in culture. In addition, corresponding paraffin sections were obtained for verification of PRLr expression by immunohistochemistry. 200 mg/L prolactin (recombinant humanM-BM- prolactin, Cat. No. JM-4687-50, MBL Woburn, MA) was added to 1M-CM-^W 10^6 attached parathyroid tumour cells. Cells were harvested using RNAlater (QIAGEN) and homogenized with QIAshredder for RNA extraction after 3 h and 24 h in culture, respectively. Negative controls were collected in parallel with each case at the same time points. RNA was extracted using QIA Cube, and quality assessed with Bioanalyser and Nanodrop. Expression array profiling and data analysis was done at the KI core facility Bioinformatics and Expression Analysis (BEA, Novum, Huddinge) using the Affymetrix platform and the TITAN ST 1.1 array. A total of 16 samples were analysed including 4 parathyroid adenomas cultured for 3 h or 24 h in the presence of prolactin plus control samples cultured in parallel without prolactin.
2012-04-30 | E-GEOD-32387 | biostudies-arrayexpress
Project description:We examined the global gene expression pattern of T cells regulated by progesterone to gain further insights into the regulatory mechanisms of progesterone. We found 325-347 cord blood T cell genes up or down-regulated by P4 in the presence or absence of exogenous TGFb1. Peripheral blood T cells were relatively unresponsive with only 30-70 genes regulated by P4. IL-6 receptor (IL-6R) expression was greatly down-regulated by progesterone in cord blood, but not PB, T cells. Overall, these differences in gene expression are consistent with the differential responses of cord blood and peripheral blood T cells to progesterone. To gain insights into the differences of progesterone and control dendritic cells, we performed a microarray study and found ~180 genes regulated by progesterone in dendritic cells. The gene expression information suggests that progesterone has the potential to alter dendritic cell responses to cytokines, chemokine production, and migration which in combination would control T cell differentiation. The CD4+ CD25- T cells were isolated from cord blood and peripheral blood and cultured in the presence and absence of progesterone 2 ug per mL, TGFb1 150 pg/mL and IL-2 100u/mL for 5-6 days. T cells from cord blood and peripheral blood were compared.
2012-03-02 | E-GEOD-22025 | biostudies-arrayexpress
Project description:Primary hyperparathyroidism is a common endocrine disorder frequently affecting postmenopausal women. In this study we have investigated expression of the prolactin receptor (PRLr) in a panel of 37 sporadic parathyroid tumours, as well as functionality in vitro in cultured parathyroid tumour cells. High levels of the prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues as compared to other reference tissues and breast cancer cells. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours PRLr immunoreactivity was observed in cytoplasm in all cases and in addition in the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim PRLr was expressed in cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells prolactin stimulation was associated with transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signaling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumors was significantly inversely correlated with plasma total Ca2+ levels. In conclusion, the prolactin receptor was found highly abundant in human parathyroid gland, parathyroid tumours, correlated with patient Ca2+ levels and functionally responsive to physiological levels of prolactin. These findings suggest a role for the prolactin receptor in human parathyroid adenomas.
2012-05-01 | GSE32387 | GEO