Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma

Wade R. Gutierrez; Jeffrey D. Rytlewski; Amanda Scherer; Grace A. Roughton; Nina C. Carnevale; Krisha Y. Vyas; Gavin R. McGivney; Qierra R. Brockman; Vickie Knepper-Adrian; Rebecca D. Dodd

doi:10.3390/cimb45020080

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Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma

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Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma

Wade R. Gutierrez, Jeffrey D. Rytlewski, Amanda Scherer, Grace A. Roughton, Nina C. Carnevale, Krisha Y. Vyas, Gavin R. McGivney, Qierra R. Brockman, Vickie Knepper-Adrian and Rebecca D. Dodd

Current issues in molecular biology, Vol.45(2), pp.1218-1232

02/02/2023

DOI: 10.3390/cimb45020080

PMCID: PMC9955904

PMID: 36826025

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Abstract

Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at understanding tumor biology and developing new, improved therapies. Though several models exist, many common mutations found in human rhabdomyosarcoma tumors remain unmodeled and understudied. This study describes a new model of embryonal rhabdomyosarcoma driven by the loss of Nf1 and Ink4a/Arf, two mutations commonly found in patient tumors. We find that this new model is histologically similar to other previously-published rhabdomyosarcoma models, although it substantially differs in the time required for tumor onset and in tumor growth kinetics. We also observe unique sex-dependent phenotypes in both primary and newly-developed orthotopic syngeneic allograft tumors that are not present in previous models. Using in vitro and in vivo studies, we examined the response to vincristine, a component of the standard-of-care chemotherapy for RMS. The findings from this study provide valuable insight into a new mouse model of rhabdomyosarcoma that addresses an ongoing need for patient-relevant animal models to further translational research.

Arf

cancer

Ink4a

mouse model

Nf1

rhabdomyosarcoma

sarcoma

vincristine

Details

Title: Subtitle: Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
Creators: Wade R. Gutierrez - University of Iowa
Jeffrey D. Rytlewski - University of Iowa
Amanda Scherer - University of Iowa
Grace A. Roughton - University of Iowa
Nina C. Carnevale - University of Iowa
Krisha Y. Vyas - University of Iowa
Gavin R. McGivney - University of Iowa
Qierra R. Brockman - University of Iowa
Vickie Knepper-Adrian - University of Iowa
Rebecca D. Dodd - University of Iowa
Resource Type: Journal article
Publication Details: Current issues in molecular biology, Vol.45(2), pp.1218-1232
DOI: 10.3390/cimb45020080
PMID: 36826025
PMCID: PMC9955904
NLM abbreviation: Curr Issues Mol Biol
ISSN: 1467-3037
eISSN: 1467-3045
Publisher: MDPI
Grant note: T32 GM067795; T32 GM007337 / University of Iowa Sarcoma Multidisciplinary Oncology Group P30 CA086862 / University of Iowa Holden Comprehensive Cancer Center University of Iowa Dance Marathon Funding American Cancer Society Research Scholar Award
Language: English
Date published: 02/02/2023
Academic Unit: Microbiology and Immunology; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984368420202771

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