A Shift from Nuclear to Cytoplasmic Breast Cancer Metastasis Suppressor 1 Expression Is Associated with Highly Proliferative Estrogen Receptor-Negative Breast Cancers

Abstract

Background/Aims: To determine breast cancer metastasis suppressor 1 (BRMS1) expression in breast cancers and the efficacy of BRMS1 as a prognostic indicator, BRMS1 expression was assessed in two sets of breast cancer tissues. Methods: Epithelial cells from 36 frozen samples of breast cancers and corresponding normal breast were collected by laser capture microdissection and assessed for BRMS1 by quantitative RT-PCR and immunohistochemistry. BRMS1 was also evaluated by immunohistochemistry in a tissue microarray of 209 breast cancers and correlated with indicators of prognosis [estrogen receptor (ER), progesterone receptor (PR), ErbB2, p53, p27^Kip1, Bcl2 and Ki-67]. Results: BRMS1 mRNA and protein were higher in 94 and 81%, respectively, of breast cancers than in corresponding normal epithelium. BRMS1 localization was predominantly nuclear, but 60–70% of cancers also exhibited cytoplasmic immunostaining. Breast cancers with lower nuclear than cytoplasmic BRMS1 (nuclear score – cytoplasmic score ≤0; 11% of cancers) had lower ER, lower PR and higher Ki-67 expression. There was also a trend toward poorer overall survival in this group of cancers, but this was only of borderline significance (p = 0.073). In Cox proportional hazards models, loss of nuclear BRMS1 was not a significant predictor of overall survival. Conclusions: Loss of nuclear BRMS1 was associated with ER-negative cancers and a high rate of proliferation, but was not an independent indicator of prognosis.

Polymorphisms in the DNA Repair GeneERCC2/XPDand Breast Cancer Risk: A HapMap-Based Case–Control Study Among Han Women in a Chinese Less-Developed Area

“…However, this protective effect was not found for the rs3916840 and rs1799793 polymorphisms. Our current results for the rs1799793 polymorphism are consistent with prior studies showing that this SNP is not associated with breast cancer (Kuschel et al, 2005;Frolova et al, 2009;Pabalan et al, 2010). To the best of our knowledge, the loci (rs3916840 and rs238416) of these polymorphisms have not been evaluated previously with respect to breast cancer.…”

C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer

“…Similar phenomena are observed with several tumor suppressors. For example, breast cancer metastasis suppressor-1 localization was predominantly nuclear, but 60-70% of cancers also showed cytoplasmic immunostaining, and 11% of cancers showed lower nuclear than cytoplasmic breast cancer metastasis suppressor-1 expression (Frolova et al, 2009). As C10ORF97 increased p27 accumulation in the nucleus by physical interaction with JAB1, we speculated that localization of C10ORF97 in the cytoplasm may attenuate the transfer of p27 to the nucleus by interfering with the physical interaction between C10ORF97 and JAB1, because JAB1 was mainly localized in the nucleus, thereby promoting cell proliferation, the characteristic feature of cancer cells.…”

BRMS151–98 and BRMS151–84 Are Crystal Oligomeric Coiled Coils with Different Oligomerization States, Which Behave as Disordered Protein Fragments in Solution

“…Therefore, the N-terminal coiled coil should disassemble prior to performing its nuclear export function. Cellular localization is particularly relevant since it has been shown that a BRMS1 localization shift to the cytoplasm is associated with highly proliferative estrogen-receptor-negative breast cancers 15 and changes in melanoma progression. 16 Moreover, we have previously reported the crystallization of BRMS1 including residues 51 to 84 17 and did not detect the hexameric oligomer association shown for BRMS1 .…”