TONSL Is an Immortalizing Oncogene and a Therapeutic Target in Breast Cancer.

ABSTRACT: Study of genomic aberrations leading to immortalization of epithelial cells has been technically challenging due to the lack of isogenic models. To address this, we used healthy primary breast luminal epithelial cells of different genetic ancestry and their hTERT-immortalized counterparts to identify transcriptomic changes associated with immortalization. Elevated expression of TONSL (Tonsoku-like, DNA repair protein) was identified as one of the earliest events during immortalization. TONSL, which is located on chromosome 8q24.3, was found to be amplified in approximately 20% of breast cancers. TONSL alone immortalized primary breast epithelial cells and increased telomerase activity, but overexpression was insufficient for neoplastic transformation. However, TONSL-immortalized primary ce

SUBMITTER: Khatpe AS 

PROVIDER: S-EPMC10107402 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature