Identification of genes induced by BRCA1 in breast cancer cells
Author
Atalay, Arzu
Advisor
Yuluğ, Işık G.
Date
2002Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
Inherited mutations of the BRCA1 gene predispose to cancer of the breast, ovaries
and other organs. The BRCA1 protein product is implicated in the maintenance of
chromosomal integrity as BRCA1-deficient cells display gross chromosomal
rearrangements. Chromosomal instability in BRCA1-deficient cells is related to
inappropriate DNA double-strand break repair. The role of the BRCA1 gene in the
maintenance of chromosomal integrity is linked to a number of biological properties
of its protein product including transcriptional regulation. The aim of this study is to
identify genes that are regulated by BRCA1. Initial attempts to overexpress BRCA1
in breast cancer cells with the tightly-regulated ecdysone inducible system did not
result in the desired levels of BRCA1 protein and ectopic BRCA1 expression was
therefore performed by using the constitutive expression vector. In this study, we have
identified genes whose expression levels are upregulated as a result of BRCA1
overexpression in MCF7 breast carcinoma cells by using the suppression subtractive
hybridisation (SSH) method. Differential screening, sequencing and homology search
studies showed that BRCA1 overexpression in breast cancer cells leads to
transcriptional upregulation of distinct classes of genes encoding proteins involved in
cellular processes such as DNA repair, chromosome assembly and segregation, signal
transduction, RNA surveillance, ubiquitin-mediated proteolysis, amino acid transport,
RNA metabolism and glucose metabolism. This study is the first to report BRCA1-
induced genes in breast carcinoma cells with the SSH technique. The identified genes
in this study may provide new insights into the tumour suppressor functions of
BRCA1.