CDKN2A Depletion Causes Aneuploidy and Enhances Cell Proliferation in Non-Immortalized Normal Human Cells

Abstract

Aneuploidy is a common feature of cancer cells and may contribute to cellular transformation and cancer development. In this study, we found that significant down-regulation of CDKN2A, CHEK2, CDCA8, TP53BP1, and CCNDBP1 led to chromosome imbalances in two diploid non-immortalized human cell lines; however, only CDKN2A inhibition enhanced cell proliferation and additionally up-regulated three cell cycle control genes: CDCA8, AURKA, and CCND. These results confirm that CDKN2A is a tumor suppressor gene driving human cancer development by inducing cell aneuploidy and cell cycle up-regulation.

KEYWORD:

• Aneuploidy
• CDKN2A lost
• Non-immortalized normal human cells

Acknowledgments

Z. Hélias-Rodzewicz received a fellowship from the Institut National du Cancer (TAKIMAGI). We are grateful to Dr. Ch. Dani for the hMADS3 cell line and to technicians from the pathology and hematology departments of Ambroise Paré Hospital for their technical support.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.