Estrogen and Breast Cancer: Understanding the Complex Interaction One Gene at a Time

Estrogen is a steroid hormone that acts in the body in both beneficial and detrimental ways. It plays a crucial role in many human processes including coagulation, bone formation, and development of sexual organs. However, estrogen is also associated with the proliferation of breast cancer. Estrogen activates the estrogen receptor (ER), a ligand-dependent transcription factor that regulates gene expression by binding to specific DNA elements and promoting or repressing transcription

Gene Expression of Down-regulated Estrogen Receptor Target Genes in Human Breast Cancer Cells following Drug Rreatment

Breast cancer is the most prevalent type of cancer found in women and the majority of such cancers are estrogen receptor (ER) positive. This means the cancer is dependent on estrogen for growth. In such cancers, ER acts as a ligand-dependent transcription factor, changing gene expression when bound to estrogen. The altered expression of ER target genes in breast cancer is a likely cause of the uncontrolled cell growth

Binding Site Sequence Motifs Estrogen Receptor Mediation of Transcriptional Repression by Interactions Determined by Cis-Regulatory DNA Sequences

Breast cancer is the second-leading cause of cancer deaths in women in the United States and affects millions each year. Much of the current research on hormonal regulation in breast cancer systems focuses on up-regulation of genes (increased rates of transcription) by estrogen receptors (ERs); however, repression, or down-regulation, of genes can also play a significant role in estrogen-responsive expression of genes. (Lin et al., 2004) Since the mechanisms of down-regulation, or gene repression, have not been well-studied, information on repression becomes a foundation for potential future application of hormonal down-regulation to other cancer systems and biological processes

The Role of Specific Estrogen-responsive Genes in Breast Cancer Development

Estrogen plays a role in the reproductive maturation of females, including breast development. It is also known that estrogen affects the development of malignant breast tumors. Estrogen works by binding to specific estrogen receptors found in the cytoplasm or near the nuclear membrane. Once bound to estrogen, these receptors diffuse into the nucleus where they bind to specific DNA sequences called estrogen-response elements. They then regulate the expression of specific genes. There are two types of estrogen receptors (ER): ERα and ERβ. Only ERα has been observed to play a role in breast cancer development. Dr. Chin-Yo Lin and associates used large-scale microarray experiments to characterize the specific genes regulated by ERα in breast tumor cells. Out of 19,000 genes, 137 were observed to be either inhibited or activated by ERα

Identifying the Mechanisms of Estrogen Receptors in Human Breast Cancer Cells through Study of Direct Target Gene Expression

Estrogens, including estrodial (E2), are known to play a significant role in a number of developmental and physiological processes including the genesis and progression of breast cancer. The action of estrogens is mediated by estrogen receptors (ERs), which function as ligand-dependent transcription factors. Upon ligand binding, ERs interact with cis-regulatory elements of target genes either directly by binding to estrogen response elements or indirectly through interaction with transcription factor complexes and their respective binding sites.1 The primary objective of this project involved the knockdown, or reduction, of NCor, a co-repressor protein known to associate with ER in the presence of E2, in order to discover its effect on the expression of previously identified down-regulated genes in ER breast cancer cells

New records of two cusk eels of the genus Neobythites from Taiwan, with a northward range extension of N. australiensis Nielsen, 2002 (Actinopterygii: Ophidiiformes: Ophidiidae)

Two species of cusk eels, Neobythites australiensis Nielsen, 2002 and Neobythites japonicus Uiblein et Nielsen, 2023 were collected from southwestern and northeastern Taiwan, respectively. They represent the first record of both species from Taiwan. The former specimen represents the first record from the Northern Hemisphere, and the latter specimen represents the second record of N. japonicus. As a result, eight species of Neobythites are recognized in Taiwan. We provide a detailed description of the two specimens, comparison with other available specimens, discussion of intraspecific variations, and a dichotomous key to species of Neobythites in Taiwan

Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites

BACKGROUND: Transcription factor binding sites (TFBS) impart specificity to cellular transcriptional responses and have largely been defined by consensus motifs derived from a handful of validated sites. The low specificity of the computational predictions of TFBSs has been attributed to ubiquity of the motifs and the relaxed sequence requirements for binding. We posited that the inadequacy is due to limited input of empirically verified sites, and demonstrated a multiplatform approach to constructing a robust model. RESULTS: Using the TFBS for the estrogen receptor (ER)α (estrogen response element [ERE]) as a model system, we extracted EREs from multiple molecular and genomic platforms whose binding to ERα has been experimentally confirmed or rejected. In silico analyses revealed significant sequence information flanking the standard binding consensus, discriminating ERE-like sequences that bind ERα from those that are nonbinders. We extended the ERE consensus by three bases, bearing a terminal G at the third position 3' and an initiator C at the third position 5', which were further validated using surface plasmon resonance spectroscopy. Our functional human ERE prediction algorithm (h-ERE) outperformed existing predictive algorithms and produced fewer than 5% false negatives upon experimental validation. CONCLUSION: Building upon a larger experimentally validated ERE set, the h-ERE algorithm is able to demarcate better the universe of ERE-like sequences that are potential ER binders. Only 14% of the predicted optimal binding sites were utilized under the experimental conditions employed, pointing to other selective criteria not related to EREs. Other factors, in addition to primary nucleotide sequence, will ultimately determine binding site selection

Transcriptional profiling of trait deterioration in the insect pathogenic nematode Heterorhabditis bacteriophora

Background: The success of a biological control agent depends on key traits, particularly reproductive potential, environmental tolerance, and ability to be cultured. These traits can deteriorate rapidly when the biological control agent is reared in culture. Trait deterioration under laboratory conditions has been widely documented in the entomopathogenic nematode (EPN) Heterorhabditis bacteriophora (Hb) but the specific mechanisms behind these genetic processes remain unclear. This research investigates the molecular mechanisms of trait deterioration of two experimental lines of Hb, an inbred line (L5M) and its original parental line (OHB). We generated transcriptional profiles of two experimental lines of Hb, identified the differentially expressed genes (DEGs) and validated their differential expression in the deteriorated line. Results: An expression profiling study was performed between experimental lines L5M and OHB of Hb with probes for 15,220 ESTs from the Hb transcriptome. Microarray analysis showed 1,185 DEGs comprising of 469 down- and 716 up-regulated genes in trait deteriorated nematodes. Analysis of the DEGs showed that trait deterioration involves massive changes of the transcripts encoding enzymes involved in metabolism, signal transduction, virulence and longevity. We observed a pattern of reduced expression of enzymes related to primary metabolic processes and induced secondary metabolism. Expression of sixteen DEGs in trait deteriorated nematodes was validated by quantitative reverse transcription-PCR (qRT-PCR) which revealed similar expression kinetics for all the genes tested as shown by microarray. Conclusion: As the most closely related major entomopathogen to C. elegans, Hb provides an attractive near-term application for using a model organism to better understand interspecies interactions and to enhance our understanding of the mechanisms underlying trait deterioration in biological control agents. This information could also be used to improve the beneficial traits of biological control agents and better understand fundamental aspects of nematode parasitism and mutualism