Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Summer Student Research Program Project Description FACULTY SPONSOR’S NAME AND DEGREE: Sylvia Christakos, Ph.D. PHONE: (973) 972 - 4033 DEPARTMENT AND INTERNAL MAILING ADDRESS: Biochemistry E667 E-MAIL:[email protected] PROJECT TITLE (200 Characters max): Examination of C/EBP alpha as a key mediator of the antiproliferative effects of 1,25 (OH) 2D3 in breast cancer HYPOTHESIS: C/EBPa is a key mediator of the antiproliferative effects of 1,25D3 in breast cancer PROJECT DESCRIPTION (Include design, methodology, data collection, techniques, data analysis to be employed and evaluation and interpretation methodology) To extend studies related to the mechanisms whereby C/EBP alpha may mediate the growth inhibitory effects of 1,25D3, experiments will be performed in MCF-7 and MDA-MB231 cells transfected with the p21 promoter in the presence of absence of 1,25D3 and C/EBP alpha expression vector (and dominant negative constructs of C/EBP alpha cofactors including components of the SWI/SNF chromatin remodeling complex) to determine regulation of p21 transcription by 1,25D3, C/EBP alpha and cofactors of C/EBP alpha in breast cancer cells. Luciferase assays will be used to measure promoter activity. Different deletions of the p21 promoter will be used in order to identify the region involved in regulation of p21 by 1,25D3 and C/EBP alpha. Changes in p21 protein and mRNA will also be examined in response to 1,25D3 in breast cancer cells. mRNA levels will be determined by quantitative PCR or Northern analysis and p21 protein will be measured by Western blot. All studies will be done in triplicate and statistically analyzed. SPONSOR’S MOST RECENT PUBLICATIONS RELEVANT TO THIS RESEARCH: Dhawan, P., Wieder, R and Christakos S. CCAAT enhancer binding protein alpha is a molecular target of 1,25-dihydroxyvitamin D3 in MCF-7 breast cancer cells. Journal of Biological Chemistry 284: in press 2009 (pre-publication available on line on pub med). IS THIS PROJECT SUPPORTED BY EXTRAMURAL FUNDS? Yes x or No (IF YES, PLEASE SUPPLY THE GRANTING AGENCY’S NAME) NIH THIS PROJECT IS: Clinical x Laboratory Behavioral Other THIS PROJECT IS CANCER-RELATED Please explain Cancer relevance: it involves mechanisms that inhibit breast cancer growth THIS PROJECT EMPLOYS RADIOISOTOPES THIS PROJECT INVOLVES THE USE OF ANIMALS no Summer Student Research Program Project Description PENDING APPROVED IACUC PROTOCOL # THIS PROJECT INVOLVES THE USE OF HUMAN SUBJECTS no PENDING APPROVED IRB PROTOCOL # M THIS PROJECT IS SUITABLE FOR: UNDERGRADUATE STUDENTS SOPHMORES in particular THIS PROJECT IS WORK-STUDY: ENTERING FRESHMAN ALL STUDENTS Yes or x medical students No x THIS PROJECT WILL BE POSTED DURING ACADEMIC YEAR FOR INTERESTED VOLUNTEERS?: Yes or No x WHAT WILL THE STUDENT LEARN FROM THIS EXPERIENCE? How to do experiments related to understanding mechanisms involved in the inhibition of breast cancer cell growth. In addition we have weekly lab meetings. The student will attend lab meetings and will present a paper from the literature related to this research. In addition the student will benefit from learning about the work of post docs and graduate students in the lab related to the vitamin D endocrine system.