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Full-Text Articles in Medicine and Health Sciences
Trim24 As An Oncogene In The Mammary Gland, Aundrietta Duncan
Trim24 As An Oncogene In The Mammary Gland, Aundrietta Duncan
Dissertations & Theses (Open Access)
Despite the many advances made in breast cancer research and treatments, breast cancer remains one of the deadliest diseases plaguing women worldwide. While many findings on genetic mutations and their role in predisposing people to breast cancer have been uncovered, we are just beginning to understand the extent to which epigenetic regulators promote tumorigenic phenotypes, metastasis, and chemotherapeutic resistance. Moreover, new experimental tools offer the ability to address questions we were previously unable to assess. My project takes advantage of a new mouse model to understand the role of a proto-oncogenic, transcriptional co-regulator, TRIM24, in mammary gland development and disease. …
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
Dissertations & Theses (Open Access)
DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …
Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang
Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang
Dissertations & Theses (Open Access)
Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important …
Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu
Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu
Dissertations & Theses (Open Access)
In this dissertation, I discovered that function of TRIM24 as a co-activator
of ERα-mediated transcriptional activation is dependent on specific histone
modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first
part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated
histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.
Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of
TRIM24-regulated ERα target genes is greatly impaired. Importantly, I
demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen
responsive elements (EREs) in a time-dependent manner upon estrogen
induction, and depletion of their expression exert corresponding time-dependent
effect …