Andrew P. Bradford Associate Professor Departments of Obstetrics & Gynecology, Biochemistry & Molecular Genetics Ph.D., (1987), Biochemistry University of Newcastle upon Tyne, England UCHSC at Fitzsimons Mail Stop 8309 RC1 North P18-5100 Phone: (303) 724-3507   Fax: (303) 724-3512 Andy.Bradford@uchsc.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 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.

Selected Publications

Reno EM, Haughian JM, Dimitrova IK, Jackson TA, Shroyer KR, Bradford AP Analysis of PKC delta expression in Endometrial Tumors. Human Pathology, 2007 in press.

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.

Latest Publications in PubMed