Aberrant expression of TopBP1 in breast cancer

Abstract

For the first time this report demonstrates aberrant expression of the TopBP1 protein in breast carcinoma. We propose TOPBP1 as a breast cancer susceptibility gene.

Regulation of p53 by TopBP1: a Potential Mechanism for p53 Inactivation in Cancer

“…Going and colleagues reported that TopBP1 is aberrantly localized to cytosol in some areas of certain breast cancer cases (out of 61 cases examined, 37 had predominantly nuclear staining, two had undetectable staining, 13 had a nuclear and nuclear-plus-cytoplasmic pattern, and nine had a nuclear-pluscytoplasmic and purely cytoplasmic pattern [10]). We also performed immunohistochemical staining on 20 formalin-fixed paraffin-embedded breast tissue sections chosen randomly from the TopBP1-overexpressing group.…”

“…Although some cells have cytoplasmic staining in addition to intense nuclear staining, we have not observed exclusively cytoplasmic distribution in these sections. To ensure that a difference in antigen retrieval techniques did not result in a different apparent distribution of TopBP1, tissues from random cases were stained separately with antigen retrieval using pH 6.0 citrate (used in the study by Going et al [10]) or pH 9.0 EDTA. The staining was less with citrate than with EDTA, but both methods demonstrated primarily nuclear patterns with little cytoplasmic staining (Fig.…”

TopBP1 in DNA Damage Response

“…Liu et al (2003) showed that deletion of the BRCT7-8 and NLS region of TopBP1 induces cytoplasmic localization of the protein. Aberrant expression and intracellular localization of TopBP1 is observed immunohistochemically in breast cancer (Going et al, 2007).…”

“…The carboxyl-terminal region of TopBP1 containing two BRCT domains shows considerable similarity to the corresponding part of BRCA1 (Going et al, 2007;Karppinen et al, 2006;Makiniemi et al, 2001;Morris et al, 2009;Yamane et al, 1997Yamane et al, , 2003. Apart from structural similarity TopBP1 shares many other common features with BRCA1.…”

“…Additionally, another repressor domain exists on the C terminus of the activation domain, which requires amino acids 586 -675. TopBP1 protein exerts its function in the nucleus and the carboxyl-terminal region of TopBP1 contains two putative nuclear localization signals (Going et al, 2007;Liu et al, 2003;Sokka et al, 2010). Liu et al (2003) showed that deletion of the BRCT7-8 and NLS region of TopBP1 induces cytoplasmic localization of the protein.…”