Single-strand
RNA-binding proteins (RBPs) are involved in many aspects of
RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in
colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other
tumor types, and the prognostic implications of
tumor-specific RBM3 expression remain unclear. Mono-specific
antibodies against RBM3 were generated. Antibody specificity was confirmed using
siRNA gene silencing, western blotting and immunohistochemistry on a panel of
breast cancer cell lines. Using tissue microarrays and IHC, RBM3
protein expression was examined in 48 normal tissues and in 20 common
cancers. Additional analysis in two independent
breast cancer cohorts (n=1016) with long-term follow-up was also carried out. RBM3 was upregulated in
cancer compared to normal tissues. The nuclear expression of RBM3 in
breast cancer was associated with low grade (P<0.001), small
tumors (P<0.001),
estrogen receptor (ER) positivity (P<0.001) and Ki-67 negativity (P<0.001) in both the
breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in
hormone receptor-positive
tumors and remained significant in multivariate interaction analysis after controlling for
tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P=0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in
breast cancer, and seems to have a specific role in ER-positive
tumors.