Basic transcription factor 3 (BTF3) regulates transcription of tumor-associated genes in pancreatic cancer cells

Abstract

Basic transcription factor 3 (BTF3) acts as a transcription factor and modulator of apoptosis, and is differentially expressed in colorectal cancer and glioblastomas. In the present study, the expression of BTF3, as well as its role in apoptosis and gene transcription, was analyzed in pancreatic ductal adenocarcinoma (PDAC). QRT-PCR, immunohistochemistry, immunoblotting, and immunofluorescence analyses were carried out to investigate BTF3 mRNA/protein expression and localization. BTF3 silencing in pancreatic cancer cells was performed using specific siRNA molecules. Functional analyses were carried out using cell growth assays, apoptosis assays, and DNA array analysis. BTF3 and BTF3a exhibited 1.3-fold and 4.6-fold increased median mRNA levels in PDAC tissues, compared to normal pancreatic tissues. BTF3 localized mainly in the cytoplasm and nuclei of tubular complexes and pancreatic cancer cells. Pancreatic cancer cell lines expressed the mRNA and protein of BTF3a (27 kDa) and BTF3b (22 kDa) isoforms. BTF3 silencing using specific siRNA molecules did not influence apoptosis induced by chemotherapy or radiotherapy. In contrast, BTF3 silencing resulted in down-regulation of several cancer-associated genes, including EPHB2, ABL2, HPSE2 and ATM, and up-regulation of KRAG, RRAS2, NFk-B, MRVI1, MADCAM1 and others. In conclusion, BTF3 is overexpressed in PDAC, where it acts as a transcriptional regulator rather than a direct modulator of apoptosis.

Paromomycin Affects Translation and Vesicle-Mediated Trafficking as Revealed by Proteomics of Paromomycin –Susceptible –Resistant Leishmania donovani

“…It has been observed that down-regulation of BTF3a is involved in inhibition of transcription and proteins synthesis in the apoptotic K562 cells [33]. It also acts as a transcriptional regulator and is associated with apoptosis and/or cell cycle arrest [34], [35]. Two of the nucleic acid associated proteins involved in RNA processing were found to be significantly down regulated in case of the PR resistant strain.…”

Fine-Mapping of 5q12.1–13.3 Unveils New Genetic Contributors to Caries

“…Hence, we focused our follow-up effort on BTF3 , since the relative expression of this gene in whole saliva was significantly associated with caries experience. BTF3 is involved in the initiation of transcription by RNA polymerase and is also involved in cell cycle regulation, apoptosis, and the transcriptional regulation of tumor-associated genes [Kusumawidjaja et al, 2007]. The protein encoded by CCNB1 is a regulatory protein involved in mitosis, and the gene product complexes with p34 (cdc2) protein kinase to form the maturation-promoting factor, which is required for cells to undergo mitosis [Brandeis et al, 1998].…”

Human Beta Casein Fragment (54–59) Modulates M. bovis BCG Survival and Basic Transcription Factor 3 (BTF3) Expression in THP-1 Cell Line

“…BTF3 has been found to be over expressed in cancer cells like sporadic colorectal cancer [31], glioblastoma multiforme [32] and pancreatic cancer cells [33], and it was argued that the down regulation of BTF3 gene in cancer cell may result in increased apoptosis of these cells, but this aspect is still under investigation. The confirmation of this fact will allow this peptide to be used as potential anti cancerous agent.…”