The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of cultured human immortalized sebocytes (SEB-1) treated with 13-cis RA was performed to gain insights into its sebocyte-specific mechanism of action. SEB-1 sebocytes were cultured with 0.1 uM 13-cis RA for 72 hours or vehicle control. Gene array expression profiling was conducted using Affymetrix HG-U95Av2 arrays in order to examine changes in gene expression as a result of treatment. A total of 85 genes (78 different genes) were significantly influenced by 13-cis RA: 58 were upregulated and 27 were down-regulated. There were changes in several genes involved in apoptosis and innate immunity. These studies are the first describing the sebocyte- specific response in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne.
Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells.
No sample metadata fields
View SamplesThe pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of skin from 8 patients treated with isotretinoin was performed to gain insights into its mechanism of action. Skin biopsies were obtained from the patients at baseline and at 8 weeks isotretinoin treatment. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays in order to examine changes in gene expression as a result of treatment. After treatment, 784 genes were significantly changed: 197 up-regulated and 587 down-regulated. The majority of genes that were up-regulated at 8 weeks encode structural proteins of the extracellular matrix such as collagens, fibulin and fibronectin. The preponderance of genes that were down-regulated at 8 weeks are involved in the metabolism of steroids, cholesterol and fatty acids.
Isotretinoin temporally regulates distinct sets of genes in patient skin.
No sample metadata fields
View SamplesThe pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of skin from 6 patients treated with isotretinoin was performed to gain insights into its mechanism of action. Skin biopsies were obtained from the patients at baseline and at one-week isotretinoin treatment. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays in order to examine changes in gene expression as a result of treatment. After treatment, 43 genes were significantly changed: 38 up-regulated and 5 down-regulated. A significant proportion of these genes are involved in pathways that regulate differentiation, tumor suppression, serine proteases, serine protease inhibitors and solute transfer. These studies are the first describing the initial changes in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne.
Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells.
No sample metadata fields
View SamplesThe pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of cultured human immortalized sebocytes (SEB-1) treated with 13-cis RA was performed to gain insights into its sebocyte-specific mechanism of action. SEB-1 sebocytes were cultured with 0.1 uM 13-cis RA for 72 hours or vehicle control. Gene array expression profiling was conducted using Affymetrix HG-U95Av2 arrays in order to examine changes in gene expression as a result of treatment. A total of 85 genes (78 different genes) were significantly influenced by 13-cis RA: 58 were upregulated and 27 were down-regulated. There were changes in several genes involved in apoptosis and innate immunity. These studies are the first describing the sebocyte- specific response in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne.
Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells.
No sample metadata fields
View SamplesHuman renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha, depending on VHL genotype and other events.
HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesIn eukaryotes, regulation of mRNA translation enables a fast, localized and finely tuned expression of gene products. Within the translation process, the first stage of translation initiation is most rigorously modulated by the actions of eukaryotic initiation factors (eIFs) and their associated proteins. These 11 eIFs catalyze the joining of the tRNA, mRNA and rRNA into a functional translation complex. Their activity is influenced by a wide variety of extra- and intracellular signals, ranging from global, such as hormone signaling and unfolded proteins, to specific, such as single amino acid imbalance and iron deficiency. Their action is correspondingly comprehensive, in increasing or decreasing recruitment and translation of most cellular mRNAs, and specialized, in targeting translation of mRNAs with regulatory features such as a 5 terminal oligopyrimidine tract (TOP), upstream open reading frames (uORFs), or an internal ribosomal entry site (IRES). In mammals, two major pathways are linked to targeted mRNA translation. The target of rapamycin (TOR) kinase induces translation of TOP and perhaps other subsets of mRNAs, whereas a family of eIF2 kinases does so with mRNAs containing uORFs or an IRES. TOR targets translation of mRNAs that code for proteins involved in translation, an action compatible with its widely accepted role in regulating cellular growth. The four members of the eIF2 kinase family increase translation of mRNAs coding for stress response proteins such as transcription factors and chaperones. Though all four kinases act on one main substrate, eIF2, published literature demonstrates both common and unique effects by each kinase in response to its specific activating stress. This suggests that the activated eIF2 kinases regulate the translation of both a global and a specific set of mRNAs. Up to now, few studies have attempted to test such a hypothesis; none has been done in mammals.
No associated publication
No sample metadata fields
View SamplesIn eukaryotes, regulation of mRNA translation enables a fast, localized and finely tuned expression of gene products. Within the translation process, the first stage of translation initiation is most rigorously modulated by the actions of eukaryotic initiation factors (eIFs) and their associated proteins. These 11 eIFs catalyze the joining of the tRNA, mRNA and rRNA into a functional translation complex. Their activity is influenced by a wide variety of extra- and intracellular signals, ranging from global, such as hormone signaling and unfolded proteins, to specific, such as single amino acid imbalance and iron deficiency. Their action is correspondingly comprehensive, in increasing or decreasing recruitment and translation of most cellular mRNAs, and specialized, in targeting translation of mRNAs with regulatory features such as a 5 terminal oligopyrimidine tract (TOP), upstream open reading frames (uORFs), or an internal ribosomal entry site (IRES). In mammals, two major pathways are linked to targeted mRNA translation. The target of rapamycin (TOR) kinase induces translation of TOP and perhaps other subsets of mRNAs, whereas a family of eIF2 kinases does so with mRNAs containing uORFs or an IRES. TOR targets translation of mRNAs that code for proteins involved in translation, an action compatible with its widely accepted role in regulating cellular growth. The four members of the eIF2 kinase family increase translation of mRNAs coding for stress response proteins such as transcription factors and chaperones. Though all four kinases act on one main substrate, eIF2, published literature demonstrates both common and unique effects by each kinase in response to its specific activating stress. This suggests that the activated eIF2 kinases regulate the translation of both a global and a specific set of mRNAs. Up to now, few studies have attempted to test such a hypothesis; none has been done in mammals.
eIF2alpha kinases GCN2 and PERK modulate transcription and translation of distinct sets of mRNAs in mouse liver.
No sample metadata fields
View SamplesIn eukaryotes, regulation of mRNA translation enables a fast, localized and finely tuned expression of gene products. Within the translation process, the first stage of translation initiation is most rigorously modulated by the actions of eukaryotic initiation factors (eIFs) and their associated proteins. These 11 eIFs catalyze the joining of the tRNA, mRNA and rRNA into a functional translation complex. Their activity is influenced by a wide variety of extra- and intracellular signals, ranging from global, such as hormone signaling and unfolded proteins, to specific, such as single amino acid imbalance and iron deficiency. Their action is correspondingly comprehensive, in increasing or decreasing recruitment and translation of most cellular mRNAs, and specialized, in targeting translation of mRNAs with regulatory features such as a 5 terminal oligopyrimidine tract (TOP), upstream open reading frames (uORFs), or an internal ribosomal entry site (IRES). In mammals, two major pathways are linked to targeted mRNA translation. The target of rapamycin (TOR) kinase induces translation of TOP and perhaps other subsets of mRNAs, whereas a family of eIF2 kinases does so with mRNAs containing uORFs or an IRES. TOR targets translation of mRNAs that code for proteins involved in translation, an action compatible with its widely accepted role in regulating cellular growth. The four members of the eIF2 kinase family increase translation of mRNAs coding for stress response proteins such as transcription factors and chaperones. Though all four kinases act on one main substrate, eIF2, published literature demonstrates both common and unique effects by each kinase in response to its specific activating stress. This suggests that the activated eIF2 kinases regulate the translation of both a global and a specific set of mRNAs. Up to now, few studies have attempted to test such a hypothesis; none has been done in mammals.
No associated publication
No sample metadata fields
View SamplesBackground: Epithelial-to-Mesenchymal Transition (EMT) is predicted to play a critical role in tumor progression and metastasis in Hepatocellular Carcinoma. Our goal was to elucidate a mechanism of tumor proliferation and metastasis using a novel murine model of EMT.
Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion.
Specimen part
View SamplesHsa-mir-365-2 is one of the two precursors that give rise to miR-365. We discovered that miR-365 directly regulates a lung cancer and developmental gene termed thyroid transcription factor 1 (TTF-1 or NKX2-1).
MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1.
Cell line
View Samples