WorldCat Identities

Horwitz, Kathryn B.

Overview
Works: 11 works in 30 publications in 1 language and 65 library holdings
Roles: Contributor, Other, Author
Classifications: RC268.2, 616.4
Publication Timeline
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Most widely held works by Kathryn B Horwitz
Endocrine aspects of cancer( Book )

5 editions published in 1993 in English and held by 34 WorldCat member libraries worldwide

Hormone Resistance and Progesterone Receptors in Breast Cancer( )

8 editions published between 1995 and 1999 in English and held by 8 WorldCat member libraries worldwide

The overall goal of the proposed research has been to understand the mechanisms by which breast cancers become resistant to hormone treatments. Specifically, the hormones involved are the steroidal agonists, estradiol and progesterone, the antagonists tamoxifen and RU-486, and the receptors to which these hormones bind, namely estrogen (ER) and progesterone receptors (PR). To this end, we initially used as models the PR of human breast cancer cells and the antiprogestin RU-486. We anticipated that the mechanisms we uncovered for progestins would be relevant to estrogens as well. This has turned out to be the case. We have discovered two proteins, which interact with antagonist-occupied receptors, and alter the direction of receptor-dependent transcription. (1) We isolated a coactivator, which we have dubbed L7/SPA, that interacts with tamoxifen-occupied ER or RU-486 occupied PR and increases transcription by 3-10 fold. It does not enhance agonist-dependent transcription, however. (2) We also isolated a corepressor protein that suppresses the partial agonist activity of tamoxifen or RU-486. These proteins may enhance (L7/SPA) or inhibit (corepressor) development of hormone resistant breast cancers, and this is now being tested in tumors taken from patients
Tamoxifen Resistant Breast Cancers: Inappropriate Transcriptional Coregulators( Book )

6 editions published between 2000 and 2002 in English and held by 6 WorldCat member libraries worldwide

To determine whether the agonist activities of tamoxifen are exaggerated in hormone-resistant breast cancers. Scope. We proposed that coregulatory proteins influence the direction of transcription by antagonist-occupied steroid receptors. We screened for such proteins, and identified three novel cDNA fragments encoding peptides that interact with antagonist-bound PRs. The aims were to clone the complete cDNAs and define their structure (Aim 1); define the role of the unknown proteins on receptor activity (Aim 2); and, if appropriate, determine the role of these proteins in hormone dependency of breast cancers (Aim 3). Major Findings - Results. We have focused on one novel cDNA fragment, designated ORF#93. In the first year we cloned the full-length cDNA; assembled its genomic structure; localized the gene to chromosome 15q26. 1; expressed the full-length protein; defined its tissue distribution; determined its subcellular localization to be cytoplasmic; and generated a polyclonal antibody that probes a 103 kDa protein. Functional studies have been started and are ongoing. The protein does not appear to have a major effect on transcription; anti sense studies have been devised to test this further. Significance. We now believe that ORF#93 has a cytoplasmic 'scaffolding' function, and allows receptors to interact with other proteins in multiprotein complexes, perhaps in association with hsp90. If so, ORF#93 may be important for cross-talk between growth factor and nuclear receptor signaling pathways
Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone( Book )

3 editions published between 2007 and 2008 in English and held by 3 WorldCat member libraries worldwide

Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the likelihood that LN metastases express receptors exceeds 80%. We developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors were tracked in living mice by whole-body imaging, and macrometastases or micrometastases were detected by intravital imaging or fluorescence microscopy. Tumor growth was estrogen dependent. To determine if the LN microenvironment alters estrogen-dependent gene expression, we developed a unique model to identify estradiol regulated genes in ER+ breast tumors and LN metastases. Fluorescent ER+ MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and PR induction were deficient in LN metastases, indicating that ER transcriptional activity was altered in the LN. Cancer cells from estradiol treated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both. Interestingly, numerous genes that were estradiol regulated in tumors lost estradiol sensitivity or were regulated in the opposite direction by estradiol in LN metastases. We propose that the LN microenvironment alters estradiol signaling and contributes to antiestrogen resistance
Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling by Mauricio P Pinto( )

1 edition published in 2014 in English and held by 2 WorldCat member libraries worldwide

Bringing estrogen receptors under control by Kathryn B Horwitz( )

1 edition published in 1999 in English and held by 2 WorldCat member libraries worldwide

Progesterone Pre-treatment Potentiates EGF Pathway Signaling in The Breast Cancer Cell Line ZR-75* by A Carvajal( )

1 edition published in 2005 in English and held by 2 WorldCat member libraries worldwide

Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells by Ndiya Ogba( )

1 edition published in 2014 in English and held by 2 WorldCat member libraries worldwide

The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells by Radhika P Ghatge( )

1 edition published in 2005 in English and held by 2 WorldCat member libraries worldwide

Modeling luminal breast cancer heterogeneity: combination therapy to suppress a hormone receptor-negative, cytokeratin 5-positive subpopulation in luminal disease by Aaron J Knox( )

1 edition published in 2014 in English and held by 2 WorldCat member libraries worldwide

Role of Nuclear Receptor Coregulators in Hormone Resistant Breast Cancer( )

2 editions published between 2000 and 2003 in English and held by 2 WorldCat member libraries worldwide

We propose that coregulatory proteins influence the direction of transcription by antagonist-occupied steroid receptors. We screened for such proteins and identified three cDNA fragments encoding peptides that interact with antagonist-bound PRs. The aims were to clone complete cDNAs; define the role of the unknown proteins on receptor activity; and determine the role of the unknown proteins in hormone dependency of breast cancers. Major findings: We have focused on one novel cDNA fragment, designated ORF#93. We cloned the full-length cDNA; localized the gene to chromosome l5q23.l; expressed the full-length protein; defined its tissue distribution; and determined that it is cytoplasmic. ORF#93 doesn't appear to have a ligand-specific effect on PR transcription, but it does have general transcriptional effects. Prom mammalian two-hybrid and GST pull-down assays, we've determined that ORF#93 interacts with hsp9O and that this is influenced by the presence of PR and its ligands. It's possible that ORF#93 functions to regulate key events in the formation of nascent PR, cytoplasmic chaperone interactions and translocation into the nucleus. If so, ORF#93 may play a key role in bringing PR to associate with cytoplasmic molecules with which PR would otherwise not interact
 
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Languages
English (30)