P18INK4C and BRCA1 inhibit follicular cell proliferation and dedifferentiation in thyroid cancer.

ABSTRACT: Only 3% of thyroid cancers are medullary thyroid carcinomas (MTCs), the rest are follicular epithelial cell derived non-MTCs (NMTCs). A dysfunctional INK4-CDK4-RB pathway is detected in most of NMTCs. DNA repair defects and genome instability are associated with NMTC dedifferentiation and aggressiveness. Whether inactivation of the INK4-CDK4-RB pathway induces NMTCs and how differentiation of NMTC cells is controlled remain elusive. In this study, we generated p18Ink4c and Brca1 singly and doubly deficient mice as well as p16Ink4a and Brca1 singly and doubly deficient mice. By using these mice and human thyroid carcinoma cell lines, we discovered that loss of p18Ink4c, not p16Ink4a, in mice stimulated follicular cell proliferation and induced NMTCs

SUBMITTER: Bai F 

PROVIDER: S-EPMC10361144 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature