Early diagnostic value of Bcl-3 localization in colorectal cancer

Abstract

BackgroundB-cell leukemia 3 (Bcl-3) is a member of the inhibitor of κB family, which regulates a wide range of biological processes by functioning as a transcriptional activator or as a repressor of target genes. Elevated expression, sustained nuclear accumulation, and uncontrolled activation of Bcl-3 causes increased cellular proliferation or survival, dependent on the tissue and type of stimuli.MethodsWe retrospectively reviewed patients who were diagnosed with colorectal cancer at Skåne University Hospital in Malmö between 1st of January 1990 and 31st of December 1991. Bcl-3 localization in colorectal cancer was assessed by immunohistochemistry on tissue microarray and freshly isolated colon from patients. Correlation between Bcl-3 localization and clinicopathological parameters of the cohort were evaluated using the Spearman rank-order correlation coefficient. In addition, Bcl-3 expression and localization in colon adenocarcinoma cells were analysed by western blot, immunohistochemistry and subcellular fractionation separately.ResultsWe found that Bcl-3 was mainly localized in the cytoplasm in the tumour tissue isolated from colon cancer patients. Normal colon samples from the same patients showed Bcl-3 localization in the nucleus. In three out of six colon cancer cell lines, we detected elevated levels of Bcl-3. In these cell lines Bcl-3 was accumulated in the cytosol. We confirmed these findings by analysing Bcl-3 localization in a colon tissue micro array consisting of 270 cases. In these samples Bcl-3 localization correlated with the proliferation marker Ki-67, but not with the apoptotic marker Caspase 3.ConclusionThese findings indicate that analysis of the subcellular localization of Bcl-3 could be a potential-early diagnostic marker in colon cancer.

BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

“…This is consistent with findings of previously studies reporting dysregulation of BCL3 expression in T/B cell leukemia [ 16 – 18 ], Hodgkin lymphoma [ 19 , 20 ], T/B cell lymphoma [ 21 , 22 ]. Apart from hematology malignancies, BCL3 has been shown to be participated in progression of diverse solid tumors, such as breast cancer [ 15 ], renal-cell carcinoma [ 13 ], non-small-cell lung cancer [ 12 ], cervical cancer [ 11 ], colorectal cancer [ 23 ]. Although dysregulation and oncogenetic roles of BCL3 in hematology malignancies are well established, the diagnostic and prognostic values of this gene are still to be evaluated.…”

“…In addition to the diagnostic value of BCL3 in cancers, prognostic value of BCL3 remains controversial in human cancers. Elevated expression of BCL3 acted as unfavorable prognostic indicator has been reported in chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, colorectal cancer, breast cancer [ 14 , 20 , 23 , 15 , 12 ]. Additionally, subcellualar location of BCL3 also is related to prognosis.…”

Immunohistochemical assessment of Survivin and Bcl3 expression as potential biomarkers for NF‐κB activation in the Barrett metaplasia–dysplasia–adenocarcinoma sequence

“…Bcl3 is a key negative feedback regulator of the NF‐κB pathway and is known to be overexpressed in different tumours such as colorectal (Saamarthy et al . ), breast (Cogswell et al . ), nasopharyngeal (Thornburg et al .…”

“…Bcl3 is a key negative feedback regulator of the NF-jB pathway and is known to be overexpressed in different tumours such as colorectal (Saamarthy et al 2015), breast (Cogswell et al 2000), nasopharyngeal (Thornburg et al 2003), endometrial (Pallares et al 2004), prostate cancer (Ahlqvist et al 2013) and cervical carcinoma (Zhao et al 2016). In addition, Bcl3 was shown to be a prognostic biomarker for inflammatory diseases such as ulcerative colitis (Reissig et al 2017).…”

BCL-3 enhances β-catenin signalling in colorectal tumour cells promoting a cancer stem cell phenotype

“…BCL-3 bears numerous tumour-promoting capabilities such as increasing proliferation [11], inflammation [12], inhibiting apoptosis [13] and promoting metastasis [14]. Importantly, studies by Puvvada et al [15] and more recently by Saamarthy et al [16] report that around 30% of colorectal tumours present with nuclear BCL-3.…”