Huntingtin Overexpression Does Not Alter Overall Survival in Murine Cancer Models

Article type: Short Communication

Authors: Chan, Laura Lynn^a | Hill, Austin^a | Lu, Ge^a | Van Raamsdonk, Jeremy^{b; c; d} | Gascoyne, Randy^{e; f} | Hayden, Michael R.^a | Leavitt, Blair R.^{a; *}

Affiliations: [a] Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada | [b] Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA | [c] Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada | [d] Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada | [e] Center for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada | [f] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Correspondence: [*] Correspondence to: Blair R. Leavitt, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Ave, Vancouver BC, V5Z 4H4, Canada. Tel.: +1 604 875 3801; Fax: +1 604 875 3840; E-mail: [email protected].

Abstract: A reduced incidence of various forms of cancer has been reported in Huntington’s disease patients and may be due to pro-apoptotic effects of mutant huntingtin. We tested this hypothesis by assessing the effects of huntingtin protein overexpression on survival in two murine cancer models. We generated YAC HD mice containing human huntingtin transgenes with various CAG tract lengths (YAC18, YAC72, YAC128) on either an Msh2 or p53 null background which have increased cancer incidence. In both mouse models of cancer, the overexpression of either mutant or wild-type huntingtin had no significant effect on overall survival. These results do not support the hypothesis that mutant huntingtin expression is protective against cancer.

Keywords: Huntington’s disease, cancer, tumorigenesis, mouse models, huntingtin, apoptosis

DOI: 10.3233/JHD-220554

Journal: Journal of Huntington's Disease, vol. 11, no. 4, pp. 383-389, 2022