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Andrew P Bradford, Associate Professor

Ph.D. (1987) University of Newcastle upon Tyne


Bradford
Department of Obstetrics & Gynecology
Division of Basic Reproductive Sciences

Mail Stop 8309, RC2, Room 3007

Phone: (303) 724 3507
Fax:     (303) 724 3512

Andy.Bradford@ucdenver.edu

My research interests focus on hormone/growth factor signaling and cancer. Specifically, our laboratory is studying the role of selective protein kinase C (PKC) isoforms in the modulation of cell growth and death in endometrial cancer. Endometrial cancer is the most common invasive gynecological malignancy in the United States. Although the annual incidence of endometrial cancer has remained relatively constant over the past decade, statistics indicate a dramatic increase in mortality, suggesting a higher prevalence of tumors, which are refractory to treatment. Thus, there is an urgent need to identify prognostic markers in endometrial cancer and to develop agents that have greater efficacy and biological specificity in the treatment of gynecological malignancies.

Recent studies from our laboratory and others suggest that members of the protein kinase C (PKC) family play critical roles in the pathogenesis of endometrial tumors, regulating both proliferation and programmed cell death (apoptosis), Moreover, PKC isozyme expression patterns may reflect the invasive or metastatic potential of endometrial cancers. Using endometrial cancer cell lines and specific adenoviral constructs, we have investigated the role of specific PKCs in etoposide-induced cell cycle arrest and apoptosis. Our results suggest that PKCα and δ exert opposing influences on proliferation and apoptosis in endometrial tumors. PKCα appears to promote proliferation and survival of endometrial cancer cells, whereas PKCδ is pro-apoptotic. Thus, PKCs are clearly important factors in the formation and progression of endometrial tumors. However, little is known regarding the molecular mechanisms underlying PKC modulation of proliferation and apoptosis in the endometrium, particularly with respect to the possible differential role of specific PKC isoforms. We postulate that specific transcriptional, mitogenic and/or apoptotic responses to PKC and isoforms may result in a more aggressive, chemotherapy-resistant endometrial tumor phenotype. Further study of PKCs in the endometrium may identify novel diagnostic/ prognostic indicators and provide new potential targets for therapeutic intervention.

We are also investigating the role of growth factor signaling and Ets transcription factors in the pathogenesis of uterine fibroids or leiomyomata.

Thorne AM, Jackson TA, Willis VC, Bradford AP. Protein Kinase C α Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells. Obstet. Gynecol. Int. 2013. In press.

Korch, C, Spillman MA, Jackson TA, Jacobsen BM, Murphy SK, Lessey BA, Jordan VC and Bradford AP. DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination. Gynecologic Oncology 2012, 127, 241-248.

​Georgieva, B, Milev, IR, Minkov, IN, Dimitrova, IK, Bradford, AP and Baev, VP. Characterization of the Uterine Leiomyoma microRNAome by Deep Sequencing. Genomics 2012. 99, 275-281.    

Bradford AP and Reyland ME. PKC and the control of Apoptosis. In "Protein Kinase C in Cancer Signaling and Therapy" Ed. Kazanietz M. 2010. 9, 189-220.    

Haughian JM and Bradford AP. Protein Kinase C alpha (PKCα) regulates growth and invasion of endometrial cancer cells. J. Cell. Physiol 2009 220:112-8.

Reno, EM, Haughian JM, Jackson TA, Thornne AM and Bradford AP. C-Jun N-terminal kinase regulates apoptosis in endometrial cancer cells. Apoptosis 2009 14:809-20.

Haughian, JM, Reno, EM, Thorne, AM and Bradford, AP. Protein Kinase C alpha dependent signaling mediates endometrial cancer cell growth and tumorigenesis. Intl. J. Cancer 2009. In press

Reno EM, Haughian JM, Dimitrova IK, Jackson,TA, Shroyer KR and Bradford AP. Analysis of Protein Kinase C Delta (PKCδ) Expression in Endometrial Tumors. Human Pathol. 2008, 39, 21-29.

Dimitrova IK, Richer JK, Rudolph MC, Spoelstra NS, Reno EM, Medina TM and Bradford AP. Gene Profiling of multiple leiomyomata ueri and matched normal tissue from a single patient. Fertility and Sterility 2009 91:2650-63.

Haughian, JM, Jackson, TA, Koterwas, DM and Bradford AP. Endometrial Cancer Cell Survival and Apoptosis is Regulated by Protein Kinase C Alpha and Delta. Endocrine-Related Cancer 2006, 13, 1-18.


 


Latest Publications in PubMed