Andrew Bradford, PhD
University of Colorado Anschutz Medical Campus
Mail Stop 8309
RC1 North P18-5100
Phone: (303) 724-3507
Fax: (303) 724-3512
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 PKCa and d exert opposing influences on proliferation and apoptosis in endometrial tumors. PKCa appears to promote proliferation and survival of endometrial cancer cells, whereas PKCd 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.
Alicia M. Thorne, Twila A. Jackson, Van C.Willis, and Andrew P. Bradford. Protein Kinase C𝛼 Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells. Obstetrics and Gynecology International (2013) in press.
Korch C, Spillman MA, Jackson TA, Jacobsen BM, Murphy SK, Lessey BA, Jordan VC, Bradford AP. DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination. Gynecol Oncol. 2012 Oct;127(1):241-8. doi: 10.1016/j.ygyno.2012.06.017. Epub 2012 Jun 16.
Iwanaga R, Wang CA, Micalizzi DS, Harrell JC, Jedlicka P, Sartorius CA, Kabos P, Farabaugh SM, Bradford AP, Ford HL. Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways. Breast Cancer Res. 2012 Jul 5;14(4):R100.
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.
Bradford AP and Reyland ME. PKC and the control of Apoptosis. In "Protein Kinase C in Cancer Signaling and Therapy" Ed. Kazanietz M. 2009 In press.
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.
Gutierrez-Hartmann, A, Duval DL, Bradford, AP ETS transcripiton factors in endocrine systems. Trends in Endcorinoloogy & Metabolism 2007, 18(4):150-8..
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.
Siriwardana G, Bradford A, Coy D, Zeitler P. Autocrine/paracrine regulation of breast cancer cell proliferation by growth hormone releasing hormone via Ras, Raf, and mitogen-activated protein kinase. Molecular Endocrinology 2006, 20 (9): 2010-2019.
Jackson TA, Koterwas DM, Bradford AP. Differential regulation of cell growth and gene expression by FGF-2 and FGF-4 in pituitary lactotroph GH4 cells. Mol Cell Endocrinol. 2006, 247(1-2):183-91.
Jackson TA, Morgan MA, Koterwas DM and Bradford AP. (2003). Fibroblast Growth Factors Regulate Prolactin Transcription via an Atypical Rac-Dependent Signaling Pathway. Mol Endocrinol. 2003 Oct;17(10):1921-30.
Tentler JJ, Bradford AP and Gutierrez-Hartmann A. (2003). Selective repression of the rat prolactin gene by stable expression of dominant-negative Ets in GH4 pituitary cells. Endocrine. 20, 3-12.
Jackson, TA, Schweppe, RE, Koterwas, DM and Bradford, AP. (2001). Fibroblast growth factor regulation of the rat prolactin promoter is mediated by protein kinase C delta. Mol. Endocrinol. 15, 1517-1528.