RB depletion is required for the continuous growth of tumors initiated by loss of RB

• Published in: PLoS genetics Vol. 17; no. 12; p. e1009941
• Main Authors: Doan, Alex, Arand, Julia, Gong, Diana, Drainas, Alexandros P, Shue, Yan Ting, Lee, Myung Chang, Zhang, Shuyuan, Walter, David M, Chaikovsky, Andrea C, Feldser, David M, Vogel, Hannes, Dow, Lukas E, Skotheim, Jan M, Sage, Julien
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.12.2021; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Biology and Life Sciences; Cell Cycle Checkpoints - genetics; Cell Line, Tumor; Disease Models, Animal; E2F Transcription Factors - metabolism; Engineering and Technology; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genetic aspects; Humans; Male; Medicine and Health Sciences; Mice; Mice, Transgenic; NIH 3T3 Cells; Pituitary Neoplasms - genetics; Pituitary Neoplasms - pathology; Research and Analysis Methods; Retinoblastoma; Retinoblastoma Binding Proteins - genetics; RNA, Small Interfering - metabolism; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1009941

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo. In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo.