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oai:www.ideals.illinois.edu:2142/24407 2023-07-10 col_2142_16508 col_2142_5131 com_2142_16507 com_2142_14793 com_2142_8903 com_2142_5130

Katzenellenbogen, Benita S. Katzenellenbogen, Benita S. Bagchi, Milan K. Katzenellenbogen, John A. Kemper, Byron W. Nardulli, Ann M. Kim, Kyuri 2011-05-25T14:38:22Z 2011-05-25T14:38:22Z 2013-05-26T10:00:25Z 2011-05-25T14:38:22Z 2011-05 Estrogens are associated with the development and progression of breast cancer in addition to their role in normal reproductive physiology, and estrogen receptors (ER) mediate the actions of estrogen in target tissues by regulating the expression of numerous biologically important target genes. The progression of human breast cancer and the development of resistance to endocrine therapies are thought to be associated with ER phosphorylation. We generated multiple combinations of ER phospho-mutants, at residues serine 104, 106, 118, 167, 236, and 305, and examined their impact on receptor half-life, the agonist and antagonist balance of selective estrogen receptor modulators (SERMs) and selective estrogen receptor downregulators (SERDs), the regulation of ER transcriptional activity, and stimulation of cell proliferation in response to estradiol and SERMs/SERD. We showed that changes in ER affecting the phosphorylation status of the receptor greatly impact receptor function and differential SERM and SERD modulated cellular responses that could contribute to resistance to endocrine therapies in breast cancer. We also studied the regulation of microRNAs (miRNAs) by estradiol and growth factors through ER and extracellular signal-regulated kinase 2 (ERK2) in order to understand their physiological impact on breast cancer. We identified nine miRNA- encoding genes harboring overlapping ER and ERK2 binding sites close to their transcription start sites, which require ER and ERK2 for transcriptional induction as well as estradiol- mediated miRNA regulation. We then identified TP63, a target of miR-101, miR-190 and miR- 196a2, and showed that TP63 plays an important role in estradiol- or growth factor-mediated cellular response in breast cancer cells (MCF-7 and MDA-MB-231) by increasing tumor cell growth and in vitro invasion mainly controlled by miR-196a2 action. These results suggest a tumor-suppressive role of miR-196a2 in regulating TP63 expression and the aggressive behavior of breast cancers. Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2011-02-15T18:56:18Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Kim_Kyuri-Thesis.doc: 1702912 bytes, checksum: e3389538df622559383236992edb31bd (MD5) Kim_Kyuri.pdf: 1186239 bytes, checksum: 56429a2284d1fc60fe63da721d6deb43 (MD5) Made available in DSpace on 2011-05-25T14:38:22Z (GMT). No. of bitstreams: 3 Kim_Kyuri.pdf: 1185673 bytes, checksum: bd8484c50966c270df7237abad9a1c25 (MD5) license.txt: 4056 bytes, checksum: 36e46229166d72080ac2c4a6a3a52826 (MD5) Kim_Kyuri-Thesis.doc: 1702400 bytes, checksum: bcf0beaa5f987cbc06de201166a7b8b4 (MD5) Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by William Ingram (wingram2@illinois.edu) on 2011-05-25T14:42:01Z Item is restricted until 2013-05-25T14:41:28Z Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2013-05-26T10:00:25Z Item was in collections: Dissertations and Theses - Molecular and Integrative Physiology (ID: 761) University of Illinois Dissertations and Theses (ID: 204) No. of bitstreams: 4 Kim_Kyuri.pdf.txt: 155692 bytes, checksum: a753c315bce9966badc2280f777ab1f4 (MD5) Kim_Kyuri.pdf: 1185673 bytes, checksum: bd8484c50966c270df7237abad9a1c25 (MD5) license.txt: 4056 bytes, checksum: 36e46229166d72080ac2c4a6a3a52826 (MD5) Kim_Kyuri-Thesis.doc: 1702400 bytes, checksum: bcf0beaa5f987cbc06de201166a7b8b4 (MD5) Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2013-05-26T10:00:25Z http://hdl.handle.net/2142/24407 en Copyright 2011 Kyuri Kim Estrogen Receptor Endocrine Resistance Breast Cancer microRNA Phosphorylation Regulation of estrogen receptor-alpha mediated gene expression and endocrine resistance through estrogen receptor-alpha phosphorylation and micro-RNA in breast cancer Molecular & Integrative Physl 1604 Molecular & Integrative Physi 0325 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Mole & Integrat Phys -UIUC 10KS0325PHD