Download Christakos, Sylvia, PhD

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.