• Akt
• PERP
• experimental carcinogenesis
• immunohistochemistry
• skin cancer

• Adhesion
• Apoptosis
• Cancer
• Inflammation
• PERP
• p53/p63

The prevalence of hepatocellular carcinoma (HCC) is still high worldwide because liver diseases could develop into HCC. Recent reports indicate nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD&NASH) and primary biliary cirrhosis and primary sclerosing cholangitis (PBC&PSC) are significant of HCC. Therefore, understanding the cellular mechanisms of the pathogenesis and hepatocarcinogenesis from normal liver cells to HCC through NAFLD&NASH or PBC&PSC is a priority to prevent the progression of liver damage and reduce the risk of further complications. By the genetic and epigenetic data mining and the system identification through next-generation sequencing data and its corresponding DNA methylation profiles of liver cells in normal, NAFLD&NASH, PBC&PSC, and HCC patients, we identified the genome-wide real genetic and epigenetic networks (GENs) of normal, NAFLD&NASH, PBC&PSC, and HCC patients. In order to get valuable insight into these identified genome-wide GENs, we then applied a principal network projection method to extract the corresponding core GENs for normal liver cells, NAFLD&NASH, PBC&PSC, and HCC. By comparing the signal transduction pathways involved in the identified core GENs, we found that the hepatocarcinogenesis through NAFLD&NASH was induced through DNA methylation of HIST2H2BE, HSPB1, RPL30, and ALDOB and the regulation of miR-21 and miR-122, and the hepatocarcinogenesis through PBC&PSC was induced through DNA methylation of RPL23A, HIST2H2BE, TIMP1, IGF2, RPL30, and ALDOB and the regulation of miR-29a, miR-21, and miR-122. The genetic and epigenetic changes in the pathogenesis and hepatocarcinogenesis potentially serve as potential diagnostic biomarkers and/or therapeutic targets.

A natural variation exists in the susceptibility to mammary cancer among wild and domestic mammalian species. Mammary stem/progenitor cells (MaSC) represent a primary target cell for transformation; however, little is known about the intrinsic response of these cells to carcinogenic insults. Polycyclic aromatic hydrocarbons (PAH), such as 7,12-dimethylbenz[a]anthracene (DMBA), are abundantly present in the environment and have been linked to the development of mammary cancer in humans and rodents. We treated MaSC from equine (mammary cancer-resistant) and canine (mammary cancer-susceptible) species with DMBA and assessed cytochrome P450 metabolic activity, DNA damage and viability. Our notable findings were that MaSC from both species showed DNA damage following DMBA treatment; however, equine MaSC initiated cell death whereas canine MaSC repaired this DNA damage. Follow-up studies, based on genome-wide transcriptome analyses, revealed that DMBA induced activation of both the intrinsic and extrinsic apoptotic pathways in equine, but not canine, MaSC. Based on these findings, we propose a hypothetical model in which undergoing apoptosis in response to an oncogenic event might contribute to a lower incidence of mammary cancer in certain mammalian species. Such a mechanism would allow for the elimination of DNA-damaged MaSC, and hence, reduce the risk of potential tumor-initiating mutations in these cells.

• DMBA
• DNA damage
• apoptosis
• mammary cancer
• mammary stem/progenitor cells

• ETS1
• ETS2
• cancer
• expression
• mutant p53
• telomerase

• R01 CA106314 NCI NIH HHS

UV radiations challenge genomic stability and are a recognized cancer risk factor. We previously found that the RNA-binding protein NONO regulates the intra-S phase checkpoint and its silencing impaired HeLa and melanoma cell response to UV-induced DNA damage. Here we investigated the mechanisms underlying NONO regulation upon UVC treatment. We found that UVC rays induce the expression of mir320a, which can indeed target NONO. However, despite mir320a induction, NONO mRNA and protein expression are not affected by UVC. We found through RNA immunoprecipitation that UVC rays induce the ubiquitous RNA-binding protein HUR to bind NONO 5′UTR in a site overlapping mir320a binding site. Both HUR silencing and its pharmacological inhibition induced NONO downregulation following UVC exposure, whereas concomitant mir320a silencing restored NONO stability. UVC-mediated mir320a upregulation is triggered by p53 binding to its promoter, which lies within a region marked by H3K4me3 and H3K27ac signals upon UVC treatment. Silencing mir320a sensitizes cells to DNA damage. Overall our findings reveal a new mechanism whereby HUR protects NONO from mir320-mediated degradation upon UVC exposure and identify a new component within the complex network of players underlying the DNA damage response adding mir320a to the list of p53-regulated targets upon genotoxic stress.

• DNA damage response
• HUR
• NONO
• mir320a
• p53

Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis. Whole genome scans revealed 663 significantly regulated genes of which 82, 47 and 25 code for stress, immune response and inflammation. Immunopathology confirmed strong induction of IgM, the complement factors C3&B, SAA, SERPING1 and others of the classical and alternate pathway. Alike, marked expression of CD205 and CD74 in Kupffer cells and lymphocytes facilitate antigen presentation and B-cell differentiation. The highly induced HIF1A and KLF6 protein expression in mast cells and macrophages sustain inflammation. Furthermore, immunogenomics discovered 24, 17, 6 and 11 significantly regulated marker genes to hallmark M1/M2 polarized macrophages, lymphocytic and granulocytic infiltrates; note, the latter was confirmed by CAE staining. Other highly regulated genes included alpha-2-macroglobulin, CRP, hepcidin, IL1R1, S100A8 and CCL20. Diclofenac treatment caused unprecedented induction of myeloperoxidase in macrophages and oxidative stress as shown by SOD1/SOD2 immunohistochemistry. Lastly, bioinformatics defined molecular circuits of inflammation and consisted of 161 regulated genes.

Altogether, the mechanism of diclofenac induced liver hypersensitivity reactions involved oxidative stress, macrophage polarization, mastocytosis, complement activation and an erroneous programming of the innate and adaptive immune system.

• CARPA
• classical and alternate pathway
• complement system
• diclofenac
• immunogenomics

• Apoptosis
• Ischemic-reperfusion injury
• Neuroprotection
• PI3K/Akt signaling pathway
• β-Caryophyllene

Chromatin architecture and dynamics are regulated by various histone and non-histone proteins. The matrix attachment region binding proteins (MARBPs) play a central role in chromatin organization and function through numerous regulatory proteins. In the present study, we demonstrate that nuclear matrix protein SMAR1 orchestrates global gene regulation as determined by massively parallel ChIP-sequencing. The study revealed that SMAR1 binds to T(C/G) repeat and targets genes involved in diverse biological pathways. We observe that SMAR1 binds and targets distinctly different genes based on the availability of p53. Our data suggest that SMAR1 binds and regulates one of the imperative microRNA clusters in cancer and metastasis, miR-371-373. It negatively regulates miR-371-373 transcription as confirmed by SMAR1 overexpression and knockdown studies. Further, deletion studies indicate that a ~200 bp region in the miR-371-373 promoter is necessary for SMAR1 binding and transcriptional repression. Recruitment of HDAC1/mSin3A complex by SMAR1, concomitant with alteration of histone marks results in downregulation of the miRNA cluster. The regulation of miR-371-373 by SMAR1 inhibits breast cancer tumorigenesis and metastasis as determined by in vivo experiments. Overall, our study highlights the binding of SMAR1 to T(C/G) repeat and its role in cancer through miR-371-373.

TP53 is one of the most frequently inactivated tumor suppressor genes in human cancer. However, unlike other tumor suppressor genes whose expression is lost, TP53 is usually inactivated as a result of a single nucleotide change within the coding region. Typically, these single nucleotide mutations result in a codon change that creates an amino acid substitution. Thus, unlike other tumor suppressor genes whose expression is lost due to genetic or epigenetic changes, the p53 gene primarily suffers missense mutations, and therefore, the cells retain and express a mutant form of the p53 protein (mtp53). It is now well established that mtp53 contributes to tumor development through its gain-of-function (GOF) activities. These GOF activities can arise from novel protein–protein interactions that can either disable other tumor suppressors (e.g., p63 and p73) or enable oncogenes such as ETS2, an ETS family member. In this review, I will focus on the identification of the mtp53/ETS2 complex and outline the diverse activities that this transcriptional regulatory complex controls to promote cancer.

• Ets2
• cancer
• p53
• transcription factors
• tumor suppressor protein p53

• Drug resistance
• EMT
• Ets1
• Triple-negative breast cancer

• Cancer
• ETS
• Regulation
• Target genes
• Transcription factors

• ETV1
• oncogenic transformation
• p14ARF
• p53
• tumor suppression

So far, investigators have found numerous tumor suppressor genes (TSGs) and oncogenes (OCGs) that control cell proliferation and apoptosis during cancer development. Furthermore, TSGs and OCGs may act as modulators of transcription factors (TFs) to influence gene regulation. A comprehensive investigation of TSGs, OCGs, TFs, and their joint target genes at the network level may provide a deeper understanding of the post-translational modulation of TSGs and OCGs to TF gene regulation.

In this study, we developed a novel computational framework for identifying target genes of TSGs and OCGs using TFs as bridges through the integration of protein-protein interactions and gene expression data. We applied this pipeline to ovarian cancer and constructed a three-layer regulatory network. In the network, the top layer was comprised of modulators (TSGs and OCGs), the middle layer included TFs, and the bottom layer contained target genes. Based on regulatory relationships in the network, we compiled TSG and OCG profiles and performed clustering analyses. Interestingly, we found TSGs and OCGs formed two distinct branches. The genes in the TSG branch were significantly enriched in DNA damage and repair, regulating macromolecule metabolism, cell cycle and apoptosis, while the genes in the OCG branch were significantly enriched in the ErbB signaling pathway. Remarkably, their specific targets showed a reversed functional enrichment in terms of apoptosis and the ErbB signaling pathway: the target genes regulated by OCGs only were enriched in anti-apoptosis and the target genes regulated by TSGs only were enriched in the ErbB signaling pathway.

This study provides the first comprehensive investigation of the interplay of TSGs and OCGs in a regulatory network modulated by TFs. Our application in ovarian cancer revealed distinct regulatory patterns of TSGs and OCGs, suggesting a competitive regulatory mechanism acting upon apoptosis and the ErbB signaling pathway through their specific target genes.

• Apoptosis/drug effects
• Apoptosis/genetics
• Cell Cycle/drug effects
• Cell Cycle/genetics
• Cluster Analysis
• Computational Biology
• Female
• Gene Expression Regulation, Neoplastic/drug effects
• Gene Regulatory Networks/drug effects
• Gene Regulatory Networks/genetics
• Genes, Tumor Suppressor
• Hormones/pharmacology
• Humans
• Oncogenes/genetics
• Ovarian Neoplasms/genetics
• Protein Interaction Maps/drug effects
• Protein Interaction Maps/genetics
• Reproduction/drug effects
• Reproduction/genetics
• Signal Transduction/drug effects
• Signal Transduction/genetics
• Transcription Factors/genetics
• Transcription Factors/metabolism

• P30 CA068485 NCI NIH HHS
• R01 LM011177 NLM NIH HHS
• R01LM011177 NLM NIH HHS
• P30CA68485 NCI NIH HHS

Autophagy is a constitutive lysosomal catabolic pathway that degrades damaged organelles and protein aggregates. Stem cells are characterized by self-renewal, pluripotency, and quiescence; their long life span, limited capacity to dilute cellular waste and spent organelles due to quiescence, along with their requirement for remodeling in order to differentiate, all suggest that they require autophagy more than other cell types. Here, we review the current literature on the role of autophagy in embryonic and adult stem cells, including hematopoietic, mesenchymal, and neuronal stem cells, highlighting the diverse and contrasting roles autophagy plays in their biology. Furthermore, we review the few studies on stem cells, lysosomal activity, and autophagy. Novel techniques to detect autophagy in primary cells are required to study autophagy in different stem cell types. These will help to elucidate the importance of autophagy in stem cells during transplantation, a promising therapeutic approach for many diseases.

• Animals
• Autophagy/physiology
• Cell Differentiation
• Cell Proliferation
• Cellular Senescence
• Humans
• Lysosomes/physiology
• Mice
• Models, Biological
• Stem Cell Transplantation
• Stem Cells/cytology
• Stem Cells/physiology

• Wellcome Trust
• BB/G021422/1 Biotechnology and Biological Sciences Research Council

• cancer
• dedifferentiation
• p53
• plasticity
• reprogramming
• stem cell

Transcription is one of the most fundamental nuclear functions and is an enzyme complex-mediated reaction that converts DNA sequences into mRNA. Analyzing DNA sequences of 5′-flanking regions of several human genes that respond to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in HL-60 cells, we have identified that the ets (GGAA) motifs are duplicated, overlapped, or clustered within a 500-bp distance from the most 5′-upstream region of the cDNA. Multiple protein factors including Ets family proteins are known to recognize and bind to the GGAA containing sequences. In addition, it has been reported that the ets motifs play important roles in regulation of various promoters. Here, we propose a molecular mechanism, defined by the presence of duplication and multiplication of the GGAA motifs, that is responsible for the initiation of transcription of several genes and for the recruitment of binding proteins to the transcription start site (TSS) of TATA-less promoters.

In a large number of studies, members of the microRNA (miRNA)-34 family such as miRNA-34a, miRNA-34b, miRNA-34c, as well as miRNA-125b and miRNA-155, have been shown to be regulators of apoptosis. The ability of these miRNAs to perform this function is mainly attributed to their ability to interact with the p53 tumor suppressor, which is a powerful regulator of the teratologic susceptibility of embryos. We chose to explore whether miRNA-34a/b/c, miRNA-125b and miRNA-155 may play a role in teratogenesis by using p53^+/- pregnant mice treated with cyclophosphamide (CP) as a model. We evaluated how CP-induced alterations in the expression of these miRNAs in the embryonic limbs correlate with embryonic p53 genotype and CP-induced limb phenotypes.

The limbs of p53 positive embryos were more sensitive to CP-induced teratogenic insult than the limbs of p53 negative embryos. The hindlimbs were more severely affected than the forelimbs. Robust miRNA-34a expression was observed in the fore- and hindlimbs of p53^+/+ embryos exposed to 12.5 mg/kg CP. The dose of 20 mg/kg CP induced almost a two-fold increase in the level of miRNA-34a expression as compared to that exhibited by p53^+/+ embryos exposed to a lower dose. Increased miRNA-34b and miRNA-34c expression was also observed. Of note, this dose activated miRNA-34a and miRNA-34c in the forelimbs of p53^-/- embryos. When embryos were exposed to 40 mg/kg CP, the expression pattern of the miRNA-34a/b/c was identical to that registered in the limbs of embryos exposed to 20 mg/kg CP. However, this dose suppressed miRNA-125b and miRNA-155 expression in the fore- and hindlimbs of p53^+/+ embryos.

This study demonstrates that teratogen-induced limb dysmorphogenesis may be associated with alterations in miRNA-34, miRNA-125b and miRNA-155 expression. It also suggests for the first time that p53-independent mechanisms exist contributing to teratogen-induced activation of miRNA-34a and miRNA-34c. At the same time, teratogen-induced suppression of miRNA-125b and miRNA-155 expression may be p53 dependent. The analysis of correlations between the expression pattern of the tested miRNAs and CP induced limb phenotypes implies that miRNAs regulating apoptosis may differ from each other with respect to their functional role in teratogenesis: some miRNAs act to protect embryos, whereas other miRNAs boost a teratogen-induced process of maldevelopment to induce embryonic death.

• Animals
• Cell Differentiation
• Cell Proliferation
• Epidermis/pathology
• Epithelial Cells/pathology
• Gene Expression Regulation
• Humans
• Matrix Metalloproteinase 13/genetics
• Mice
• Mice, Transgenic
• Neoplasms, Squamous Cell/etiology
• Proto-Oncogene Protein c-ets-1/genetics

Missense point mutations in the TP53 gene are frequent genetic alterations in human tumor tissue and cell lines derived thereof. Mutant p53 (mutp53) proteins have lost sequence-specific DNA binding, but have retained the ability to interact in a structure-selective manner with non-B DNA and to act as regulators of transcription. To identify functional binding sites of mutp53, we established a small library of genomic sequences bound by p53^R273H in U251 human glioblastoma cells using chromatin immunoprecipitation (ChIP). Mutp53 binding to isolated DNA fragments confirmed the specificity of the ChIP. The mutp53 bound DNA sequences are rich in repetitive DNA elements, which are dispersed over non-coding DNA regions. Stable down-regulation of mutp53 expression strongly suggested that mutp53 binding to genomic DNA is functional. We identified the PPARGC1A and FRMD5 genes as p53^R273H targets regulated by binding to intronic and intra-genic sequences. We propose a model that attributes the oncogenic functions of mutp53 to its ability to interact with intronic and intergenic non-B DNA sequences and modulate gene transcription via re-organization of chromatin.

Gene-set analysis evaluates the expression of biological pathways, or a priori defined gene sets, rather than that of individual genes, in association with a binary phenotype, and is of great biologic interest in many DNA microarray studies. Gene Set Enrichment Analysis (GSEA) has been applied widely as a tool for gene-set analyses. We describe here some critical problems with GSEA and propose an alternative method by extending the individual-gene analysis method, Significance Analysis of Microarray (SAM), to gene-set analyses (SAM-GS).

Using a mouse microarray dataset with simulated gene sets, we illustrate that GSEA gives statistical significance to gene sets that have no gene associated with the phenotype (null gene sets), and has very low power to detect gene sets in which half the genes are moderately or strongly associated with the phenotype (truly-associated gene sets). SAM-GS, on the other hand, performs very well. The two methods are also compared in the analyses of three real microarray datasets and relevant pathways, the diverging results of which clearly show advantages of SAM-GS over GSEA, both statistically and biologically. In a microarray study for identifying biological pathways whose gene expressions are associated with p53 mutation in cancer cell lines, we found biologically relevant performance differences between the two methods. Specifically, there are 31 additional pathways identified as significant by SAM-GS over GSEA, that are associated with the presence vs. absence of p53. Of the 31 gene sets, 11 actually involve p53 directly as a member. A further 6 gene sets directly involve the extrinsic and intrinsic apoptosis pathways, 3 involve the cell-cycle machinery, and 3 involve cytokines and/or JAK/STAT signaling. Each of these 12 gene sets, then, is in a direct, well-established relationship with aspects of p53 signaling. Of the remaining 8 gene sets, 6 have plausible, if less well established, links with p53.

We conclude that GSEA has important limitations as a gene-set analysis approach for microarray experiments for identifying biological pathways associated with a binary phenotype. As an alternative statistically-sound method, we propose SAM-GS. A free Excel Add-In for performing SAM-GS is available for public use.

• Animals
• Cell Differentiation
• Cell Proliferation
• Enhancer Elements, Genetic
• Enzyme Activation
• Extracellular Signal-Regulated MAP Kinases/metabolism
• Humans
• Mitogen-Activated Protein Kinases/metabolism
• Nerve Growth Factor/metabolism
• Neurons/cytology
• Neurons/physiology
• PC12 Cells
• Phosphorylation
• Rats
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/metabolism

• Animals
• Cell Proliferation
• Embryonic Stem Cells/cytology
• Glycolysis
• Mice
• Mice, Inbred C57BL
• Mitochondria/physiology
• Oxygen Consumption

• MC_U120085810 Medical Research Council
• Wellcome Trust

• Base Sequence
• Binding Sites
• Blotting, Western
• Cell Cycle Proteins/genetics
• Cell Line, Tumor
• DNA Primers
• Humans
• Introns
• Nuclear Proteins/genetics
• Radiation, Ionizing
• Transcription Factor AP-1/metabolism
• Transcription Factor AP-1/physiology
• Transcription, Genetic/genetics

• Animals
• Apoptosis/physiology
• Base Sequence
• Binding Sites
• COS Cells
• Caspase 1/genetics
• Caspase 1/physiology
• Cell Line, Transformed
• Cell Line, Tumor
• Chlorocebus aethiops
• Colonic Neoplasms/enzymology
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Genes, Reporter/genetics
• Humans
• Luciferases/genetics
• Mice
• Mice, Nude
• NIH 3T3 Cells
• Promoter Regions, Genetic
• Proto-Oncogene Protein c-ets-1
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins/physiology
• Proto-Oncogene Proteins c-ets
• Transcription Factors/genetics
• Transcription Factors/metabolism
• Transcription Factors/physiology
• Transcriptional Activation
• Transfection
• fas Receptor/physiology

• K22CA109577 NCI NIH HHS
• K22 CA109577 NCI NIH HHS
• R01CA109860 NCI NIH HHS
• R01 CA109860 NCI NIH HHS
• P01 CA078582 NCI NIH HHS
• R01 CA109860-03 NCI NIH HHS
• P01CA78582 NCI NIH HHS
• P01 CA078582-070005 NCI NIH HHS

• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors
• Calcium-Calmodulin-Dependent Protein Kinases/metabolism
• Cell Line
• Cell Shape
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasms/enzymology
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/pathology
• Oligonucleotide Array Sequence Analysis
• Plicamycin/analogs & derivatives
• Plicamycin/pharmacology
• Protein Kinase C/genetics
• Protein Kinase C/metabolism
• Protein Kinase C-alpha
• Proto-Oncogene Protein c-ets-1
• Proto-Oncogene Proteins/biosynthesis
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins c-ets
• RNA Interference
• Transcription Factors/biosynthesis
• Transcription Factors/genetics
• Transcription Factors/metabolism
• Ultraviolet Rays

• Animals
• Base Sequence
• DNA/genetics
• Epithelial Cells/pathology
• Female
• Fetal Development/genetics
• Fetal Development/physiology
• Gene Expression Regulation, Developmental
• Heterozygote
• Lactation
• Mammary Glands, Animal/growth & development
• Mammary Glands, Animal/pathology
• Mice
• Mice, Knockout
• Pregnancy
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Receptors, Prolactin/genetics
• Receptors, Prolactin/metabolism
• Transcription Factors/deficiency
• Transcription Factors/genetics
• Transcription Factors/physiology

• Acetyltransferases/metabolism
• Amino Acid Sequence
• Baculoviridae/genetics
• Blotting, Western
• CREB-Binding Protein
• Cell Cycle Proteins/metabolism
• Chromatography, Affinity
• Genes, Reporter
• Genes, ras
• HeLa Cells
• Histone Acetyltransferases
• Humans
• Luciferases/metabolism
• Mitogen-Activated Protein Kinases/metabolism
• Models, Biological
• Models, Molecular
• Nuclear Magnetic Resonance, Biomolecular
• Nuclear Proteins/metabolism
• Phosphorylation
• Protein Structure, Tertiary
• Proto-Oncogene Protein c-ets-1
• Proto-Oncogene Protein c-ets-2
• Proto-Oncogene Proteins/chemistry
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins c-ets
• Recombinant Proteins/metabolism
• Signal Transduction
• Silver Staining
• Trans-Activators/chemistry
• Trans-Activators/genetics
• Trans-Activators/metabolism
• Transcription Factors/chemistry
• Transcription Factors/genetics
• Transcription Factors/metabolism
• Transcriptional Activation
• p300-CBP Transcription Factors

• T32 GM008537 NIGMS NIH HHS
• CA 24014 NCI NIH HHS
• T32 CA 09602 NCI NIH HHS
• T32 DK007115 NIDDK NIH HHS
• GM 08537 NIGMS NIH HHS
• R01 GM038663 NIGMS NIH HHS
• T32 DK 07115 NIDDK NIH HHS
• P30 CA042014 NCI NIH HHS
• T32 CA009602 NCI NIH HHS

• Apoptosis
• Cell Differentiation
• Cell Enlargement
• Cells, Cultured
• Extracellular Matrix/ultrastructure
• Glycogen/analysis
• Histocytochemistry/methods
• Humans
• Image Processing, Computer-Assisted
• Immunohistochemistry/methods
• In Situ Nick-End Labeling
• Microscopy, Electron, Transmission
• Microscopy, Phase-Contrast
• Phagocytosis
• Stem Cells/chemistry
• Stem Cells/cytology
• Stem Cells/ultrastructure

• Cytochrome P-450 Enzyme System/genetics
• Cytochrome P-450 Enzyme System/metabolism
• DNA/metabolism
• DNA Helicases/genetics
• DNA Helicases/metabolism
• DNA-Binding Proteins/genetics
• DNA-Binding Proteins/metabolism
• Gene Expression Regulation/physiology
• HeLa Cells
• Humans
• Mutation
• Phosphorylation
• Proto-Oncogene Protein c-ets-1
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins c-ets
• Receptors, Calcitriol/metabolism
• Steroid Hydroxylases/genetics
• Steroid Hydroxylases/metabolism
• Transcription Factor TFIIH
• Transcription Factors/genetics
• Transcription Factors/metabolism
• Transcription Factors, TFII/metabolism
• Vitamin D/metabolism
• Vitamin D3 24-Hydroxylase
• Xeroderma Pigmentosum Group D Protein