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Department of Pathology and Laboratory Medicine
Pathology and Laboratory Medicine  :  Faculty

Faculty


Roy A. Jensen, M.D.

Roy JensenProfessor of Pathology and Laboratory Medicine
Director, University of Kansas Cancer Center
Division of Cancer and Developmental Biology

MD: Vanderbilt University  

Email: rjensen@kumc.edu
Jensen Lab web site

Ph.D. students are welcome.  Please contact me for more information.

My research interests have been with the breast cancer susceptibility gene 1 (BRCA1) and breast cancer for over 20 years.  I was part of the team to provide the first evidence that BRCA1 was a tumor suppressor.  Currently our lab has several projects aimed at understanding BRCA1 regulation and how we might enhance the ability of BRCA1 to act as a tumor suppressor.

BRCA1 has been intensely investigated and mutations in the BRCA1 gene have been found to account for half of the hereditary breast cancer cases and almost all hereditary breast and ovarian cancer cases.  Although the role of BRCA1 in sporadic breast and ovarian cancer is still uncertain, decreased BRCA1 expression often accompanies sporadic breast cancer progression.  However, data published from my lab demonstrates that the overexpression of BRCA1 in the murine mammary gland provides protection against mutagen-induced mammary neoplasia.  This work supports the hypothesis that an increase in BRCA1 can provide protection against tumors.  Therefore, one project in the laboratory developed a stable human breast cancer cell line containing integrated copies of a BRCA1 promoter-driven luciferase reporter plasmid and screened over 100,000 compounds for their ability to increase BRCA1 expression.  The overall objective of this project is to identify a drug that will increase BRCA1 and restore its tumor suppressor activity. This project shows promise for the discovery of a new agent to prevent or treat breast cancer.

Another project in the lab aims to identify cellular components as regulators of BRCA1 expression and function.  DNA damage repair is a critical BRCA1 function that has been extensively investigated and is the focus of our cell-based functional assay developed to identify potential regulatory kinases of BRCA1 expression and function. DNA damage leads to the localization of several proteins involved in the repair of DNA, including BRCA1 and these repair sites are visualized as nuclear foci using fluorescence-based microscopy. Additionally, kinases modulate a variety of cell-specific responses, including signal transduction and DNA damage repair. These kinases can be selectively targeted for knockdown using siRNA to investigate the effect of a kinase on BRCA1 foci formation. Changes in either BRCA1 expression or activity will be reflected in observable alterations in BRCA1 foci formation. We have established the experimental parameters of the functional assay and are currently screening an siRNA kinase library for regulators of BRCA1 expression.

Additionally, BRCA1 has been shown to have a role in stem cell regulation.  We are furthering those studies to understand the mechanisms behind breast cancer stem cells and expression of BRCA1. 

My lab research aims at understanding BRCA1 regulation, expression and function.  We hope our contributions to the BRCA1 and breast cancer fields will ultimately result in new preventative or therapeutic treatment options for breast cancer patients.

Selected Publications:

  1. Rizki A, Weaver VM, Lee SY, Rozenberg GI, Chin K, Myers CA, Bascom JL, Mott JD, Semeiks JR, Grate LR, Mian IS, Borowsky AD, Jensen RA, Idowu MO, Chen F, Chen DJ, Petersen OW, Gray JW, Bissell MJ:  A human breast cell model of preinvasive to invasive transition.  Cancer Research 68(5): 1378-1387, 2008.
  2. Hoshino A, Yee CJ, Campbell M,  Woltjer RL Townsend  RL, van der Meer R, Shyr Y, Holt JT, Moses HL, and Jensen  RA: Effects of BRCA1 Transgene Expression on Murine  Mammary Gland Development and Mutagen-Induced Mammary Neoplasia. International Journal of Biological Science 3(5): 281-291, 2007.
  3. McLaren BK, Schuyler PA, Sanders ME, Jensen RA, Simpson JF, Dupont WD, Page DL. Excellent survival, cancer type, and Nottingham grade after atypical lobular hyperplasia on initial breast biopsy.  Cancer. 2006 Sep 15;107(6):1227-33.
  4. Chaurand P, Sanders ME, Jensen RA, Caprioli RM.  Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections.  Am J Pathol. 2004 Oct;165(4):1057-68. Review.
  5. Kasami M, Jensen RA, Simpson JF, Page DL. Lobulocentricity of breast hypersecretory hyperplasia with cytologic atypia: infrequent association with carcinoma in situ.  Am J Clin Pathol. 2004 Nov;122(5):714-20.
  6. Yamagata N, Shyr Y, Yanagisawa K, Edgerton M, Dang TP, Gonzalez A, Nadaf S,Larsen P, Roberts JR, Nesbitt JC, Jensen RA, Levy S, Moore JH, Minna JD, Carbone DP.  A training-testing approach to the molecular classification of resectednon-small cell lung cancer.  Clin Cancer Res. 2003 Oct 15;9(13):4695-704.
  7. Gorska AE, Jensen RA, Shyr Y, Aakre ME, Bhowmick NA and Moses HL:  Transgenic Mice Expressing a Dominant-Negative Mutant Type II TGF-B Receptor Exhibit Impaired Mammary Development and Enhanced Mammary Tumor Formation.  American Journal of Pathology 163: 1539-1549, 2003.
  8. Page DL, Lagios MD, and Jensen RA.  “In Situ Carcinomas of the Breast,” in The Breast: Comprehensive Management of Benign and Malignant Diseases, 3rd edition, editors, Bland KI and Copeland EM, WB Saunders, New York, 2003, pages 255-278.
  9. Campbell M, Qu S, Wells S, Sugandha H, and Jensen RA:  An adenoviral vector containing an Arg-Gly-Asp (RGD)-integrin binding motif in the fiber knob enhances protein product levels from transgenes refractory to expression.  Cancer Gene Therapy 10:  559-570, 2003. 
  10. Jensen RA, and Page DL:  Ductal Carcinoma in situ of the Breast:  Impact of Pathology on Therapeutic Decisions.  American Journal of Surgical Pathology 27: 828-831, 2003.
  11. Page DL, Schuyler, PA, Dupont WD, Jensen RA, Plummer WD, and Simpson JF: Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study.  Lancet 361: 125-129, 2003. 
  12. Xu BJ, Sanders ME, Jensen RA, and Caprioli RM:  Direct Analysis of Laser Capture Microdissected Cells by MALDI Mass Spectrometry.  Journal of the American Society of Mass Spectrometry 13: 1292-1297, 2002.
  13. Campbell M, Aprelikova ON, van der Meer R, Yee CJ, Woltjer RL, Liu ET, and Jensen RA:  Construction and Characterization of Recombinant Adenoviruses Expressing Human BRCA1 or Murine Brca1 Genes.  Cancer Gene Therapy 8:  1-9, 2001.
  14. Page DL, Jensen RA, Simpson JF, and Dupont WD:  Historical and Epidemiologic Background of Human Premalignant Breast Disease. Journal of Mammary Gland Biology and Neoplasia 5: 341-349, 2000. 
  15. Cardiff RD, Moghanaki D, and Jensen RA:  Genetically Engineered Mouse Models of Mammary Intraepithelial Neoplasia.  Journal of Mammary Gland Biology and Neoplasia 5:  421-437, 2000. 
  16. Anver M, Cardiff RD, Gusterson B, Green J, Heninghausen L, Jensen RA, Merino MJ, Rehm S, Russo J, Tavassoli FA, Ward JM, and Wakefield LM.  The Mammary Pathology Of Genetically Engineered Mice:  The consensus report and recommendations from the Annapolis Meeting.  Oncogene 19:  968-988, 2000.
  17. Aprelikova ON, Fang BS, Meissner EG, Cotter S, Campbell M, Kuthiala A, Bessho M, Jensen RA, and Liu ET.  BRCA1 Associated Growth Arrest is RB Dependent.  Proceedings of The National Academy of Sciences 96: 11866-11871, 1999.
  18. Abbott DW, Thompson ME, Robinson-Benion C, Thomlinson G, Jensen RA, and Holt JT:  BRCA1 expression restores radiation resistance in BRCA1-defective cancer cells through enhancement of transcription coupled DNA repair.  Journal of Biological Chemistry 274:  18808-18812, 1999.
  19. Dupont WD, Page DL, Parl FF, Plummer WD, Schuyler P, and Kasami M, Jensen RA:  Estrogen Replacement Therapy in Women with Previous Histologically Defined Breast Lesions.  Cancer 85:  1277-1283, 1999.
  20. Page DL, Simpson JF, and Jensen RA:  Nomenclature of Ductal Carcinoma in situ.  Journal of the National Cancer Institute 90:  1015-1016, 1998. 
  21. Tait DL, Obermiller PS, Redlin-Frazier S, Jensen RA, Welsch P, Dann J, King M-C, Johnson DH, and Holt JT:  A Phase I Trial of Retroviral BRCA1sv Gene Therapy in Ovarian Cancer.  Clinical Cancer Research 3:  1959-1968, 1997.
  22. Jensen RA and Page DL:  Genetic Testing and Informed Consent.  JAMA 278:  821, 1997. 
  23. Page DL, and Jensen RA:  Ductal Carcinoma in situ-Understanding the Misunderstood Stepchild.  JAMA, 275:  948-949, 1996.
  24. Holt JT, Thompson ME, Szabo CI, Robinson-Benion C, Arteaga CL, King M-C, and Jensen RA:  Growth Retardation and Tumor Inhibition by BRCA1.  Nature Genetics 12:  298-302, 1996.
  25. Page DL, Dupont WD, Jensen RA, and Schyler P:  Continued Local Recurrence of Carcinoma 15-25 Years After Biopsy Only for Low Grade Ductal Carcinoma In Situ of the Breast.  Cancer 76:  1197-1200, 1995.
  26. Thompson, ME, Jensen RA, Obermiller PS, Page DL, and Holt JT:  Decreased expression of BRCA1 accelerates growthand is frequently present during sporadic breast cancer progression.  Nature Genetics, 9:  444-450, 1995.
  27. Jensen RA, Page DL, and Holt JT:  Identification of genes expressed in premalignant breast disease.  Proceedings of the National Academy of Sciences, 91:  9257-9261, 1994.
  28. Jensen RA, Page DL, Dupont WD, and Rogers LW:  Invasive Breast Cancer Risk in Women with Sclerosing Adenosis.  Cancer, 64:  1977-1983,1989.
  29. Jensen RA, Marshak D, Anderson C, Lucas TJ, and Watterson DM:  Characterization of Human Brain S100 Protein Fraction:  Amino Acid Sequence of S100. Journal of Neurochemistry, 45:  700-705, 1985.