Bisphenol A-induced DNA damages promote to lymphoma progression in human lymphoblastoid cells through aberrant CTNNB1 signaling pathway

Summary Lymphoma is a group of blood cancers that develop from the immune system, and one of the main risk factors is associated with exposure to environmental chemicals. Bisphenol A (BPA) is a common chemical used in the manufacture of materials in polycarbonate and epoxy plastic products and can interfere with the immune system. BPA is considered to possibly induce lymphoma development by affecting the immune system, but its potential mechanisms have not been well established. This study performed a gene-network analysis of microarray data sets in human lymphoma tissues as well as in human cells with BPA exposure to explore module genes and construct the potential pathway for lymphomagenesis in response to BPA. This study provided evidence that BPA exposure resulted in disrupted cell cycle and DNA damage by activating CTNNB1, the initiator of the aberrant constructed CTNNB1-NFKB1-AR-IGF1-TWIST1 pathway, which may potentially lead to lymphomagenesis.
Graphical abstract
Highlights • CTNNB1 is an initiator of BPA-mediated lymphomagenesis by gene-network analysis • BPA exposure promotes clonogenic survival of damaged TK6 lymphoblastoid cells • BPA/CTNNB1 dysregulates DNA-repair-associated genes TP53 and CDKN1A • BPA-/CTNNB1-mediated lymphomagenesis is attributable to DNA breaks and G2/M arrest
Molecular biology; Cancer