Publications by authors named "Takita Felder Sumter"

4 Publications

  • Page 1 of 1

The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer.

Cell Biochem Funct 2013 Apr 7;31(3):228-36. Epub 2012 Sep 7.

Department of Chemistry, Physics, and Geology, Winthrop University, Rock Hill, SC 29733, USA.

High-mobility group A1 (HMGA1) encodes proteins that act as mediators in viral integration, modification of chromatin structure, neoplastic transformation and metastatic progression. Because HMGA1 is overexpressed in most cancers and has transcriptional relationships with several Wnt-responsive genes, we explored the involvement of HMGA1 in Wnt/β-catenin/TCF-4 signalling. In adenomatous polyposis coli (APC(Min/+)) mice, we observed significant up-regulation of HMGA1 mRNA and protein in intestinal tumours when compared with normal intestinal mucosa. Conversely, restoration of Wnt signalling by the zinc induction of wild-type APC resulted in HMGA1 down-regulation in HT-29 cells. Because APC mutations are associated with mobilization of the β-catenin/TCF-4 transcriptional complex and subsequent activation of downstream oncogenic targets, we analyzed the 5'-flanking sequence of HMGA1 for putative TCF-4 binding elements. We identified two regions that specifically bind the β-catenin/TCF-4 complex in vitro and in vivo, identifying HMGA1 as an immediate target of the β-catenin/TCF-4 signalling pathway in colon cancer. Collectively, these findings strongly implicate Wnt/β-catenin/TCF-4 signalling in regulating HMGA1 to further expand the extensive regulatory network affected by Wnt/β-catenin/TCF-4 signalling.
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http://dx.doi.org/10.1002/cbf.2876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616152PMC
April 2013

An approach to teaching general chemistry II that highlights the interdisciplinary nature of science.

Biochem Mol Biol Educ 2011 Mar-Apr;39(2):110-6

Department of Chemistry, Winthrop University, Rock Hill South Carolina 29733, USA.

The need for a revised curriculum within the life sciences has been well-established. One strategy to improve student preparation in the life sciences is to redesign introductory courses like biology, chemistry, and physics so that they better reflect their disciplinary interdependence. We describe a medically relevant, context-based approach to teaching second semester general chemistry that demonstrates the interdisciplinary nature of biology and chemistry. Our innovative method provides a model in which disciplinary barriers are diminished early in the undergraduate science curriculum. The course is divided into three principle educational modules: 1) Fundamentals of General Chemistry, 2) Medical Approaches to Inflammation, and 3) Neuroscience as a connector of chemistry, biology, and psychology. We accurately anticipated that this modified approach to teaching general chemistry would enhance student interest in chemistry and bridge the perceived gaps between biology and chemistry. The course serves as a template for context-based, interdisciplinary teaching that lays the foundation needed to train 21st century scientists.
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http://dx.doi.org/10.1002/bmb.20465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049001PMC
July 2011

The high-mobility group A1a/signal transducer and activator of transcription-3 axis: an achilles heel for hematopoietic malignancies?

Cancer Res 2008 Dec;68(24):10121-7

Departments of Medicine, Hematology Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Although HMGA1 (high-mobility group A1; formerly HMG-I/Y) is an oncogene that is widely overexpressed in aggressive cancers, the molecular mechanisms underlying transformation by HMGA1 are only beginning to emerge. HMGA1 encodes the HMGA1a and HMGA1b protein isoforms, which function in regulating gene expression. To determine how HMGA1 leads to neoplastic transformation, we looked for genes regulated by HMGA1 using gene expression profile analysis. Here, we show that the STAT3 gene, which encodes the signaling molecule signal transducer and activator of transcription 3 (STAT3), is a critical downstream target of HMGA1a. STAT3 mRNA and protein are up-regulated in fibroblasts overexpressing HMGA1a and activated STAT3 recapitulates the transforming activity of HMGA1a in fibroblasts. HMGA1a also binds directly to a conserved region of the STAT3 promoter in vivo in human leukemia cells by chromatin immunoprecipitation and activates transcription of the STAT3 promoter in transfection experiments. To determine if this pathway contributes to HMGA1-mediated transformation, we investigated STAT3 expression in our HMGA1a transgenic mice, all of which developed aggressive lymphoid malignancy. STAT3 expression was increased in the leukemia cells from our transgenics but not in control cells. Blocking STAT3 function induced apoptosis in the transgenic leukemia cells but not in controls. In primary human leukemia samples, there was a positive correlation between HMGA1a and STAT3 mRNA. Moreover, blocking STAT3 function in human leukemia or lymphoma cells led to decreased cellular motility and foci formation. Our results show that the HMGA1a-STAT3 axis is a potential Achilles heel that could be exploited therapeutically in hematopoietic and other malignancies overexpressing HMGA1a.
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http://dx.doi.org/10.1158/0008-5472.CAN-08-2121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913892PMC
December 2008

The HMG-I oncogene causes highly penetrant, aggressive lymphoid malignancy in transgenic mice and is overexpressed in human leukemia.

Cancer Res 2004 May;64(10):3371-5

Hematology Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

HMG-I/Y is overexpressed in human cancer, although a direct role for this gene in transformation has not been established. We generated transgenic mice with HMG-I targeted to lymphoid cells. All seven informative founder HMG-I mice developed aggressive lymphoma by a mean age of 4.8 months. Tumors express T-cell markers and are transplantable. We also demonstrate that HMG-I mRNA and protein are increased in human acute lymphocytic leukemia samples. Our results show that HMG-I functions as an oncogene and suggest that it contributes to the pathogenesis of leukemia and other cancers with increased HMG-I expression.
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http://dx.doi.org/10.1158/0008-5472.CAN-04-0044DOI Listing
May 2004