Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer

Abstract

B-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. As high levels of Bcl-3 expression and activation have been detected in different types of human cancer, Bcl-3 has been labeled a proto-oncogene. Our study uncovered a markedly upregulated Bcl-3 expression in human prostate cancer (PCa), where inflammatory cell infiltration was observed. Elevated Bcl-3 expression in PCa was dependent on the proinflammatory cytokine interleukin-6-mediated STAT3 activation. Microarray analyses, using Bcl-3 knockdown in PCa cells, identified the inhibitor of DNA-binding (Id) family of helix-loop-helix proteins as potential Bcl-3-regulated genes. Bcl-3 knockdown reduced the abundance of Id-1 and Id-2 proteins and boosted PCa cells to be more receptive to undergoing apoptosis following treatment with anticancer drug. Our data imply that inactivation of Bcl-3 may lead to sensitization of cancer cells to chemotherapeutic drug-induced apoptosis, thus suggesting a potential therapeutic strategy in PCa treatment.

Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients

“…The immunohistochemical analysis of BCL3 protein revealed statistically significant higher expression levels in neoplastic tissues compared to tumor-adjacent, normal lung specimens where no signal was detected. This finding is consistent with published data reporting deregulation of BCL3 expression in other solid tumors such as breast cancer [12][13][14][15], prostate cancer [16], nasopharygeal carcinomas [17], endometrial tumors [18] and colorectal cancer [19]. The overexpression of BCL3 in all histological subtypes and all stages of NSCLC may reflect the decisive role that this molecule plays in lung carcinogenesis and tumor progression.…”

“…In addition, BCL3 has been documented to be deregulated in a number of solid tumors including breast cancer [12][13][14][15], prostate cancer [16], nasopharygeal carcinomas [17], endometrial tumors [18] and colorectal cancer [19].…”

G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma

“…STAT3 functions as a critical regulator of oncogenic signaling through manipulation of activation of transcriptional genes [54], such as Bcl-2 family, cyclin D1, and VEGF. Furthermore, STAT3 is required for the activation of proto-oncogenes, such as Bcl-2 and Bcl-3, which will avoid cell apoptosis [55][56][57]. Most notably, G6PD was found to regulate the proliferation and apoptosis of human melanoma by STAT3/STAT5 signaling pathway [58], implying the important associations of G6PD with STATs signaling pathway.…”

NF-κB-induced KIAA1199 promotes survival through EGFR signalling

“…BCL-3 is overexpressed in a variety of haematological tumours and is oncogenic, as evidenced by its ability to transform NIH3T3 cells, to induce MDM2 and to protect from ultraviolet-mediated apoptosis19202122232425. Aberrant BCL-3 expression has also been reported in breast, nasopharyngeal and prostate cancers, and in hepatocarcinomas26272829. Finally, increased nuclear BCL-3 levels cause enhanced keratinocyte proliferation in familial cylindromatosis, a genetic disease characterized by benign tumours of hair-follicle keratinocytes that results from loss-of-function mutations of CYLD, a deubiquitinating enzyme limiting BCL-3 nuclear levels3031.…”