e-Article
Molecular cytogenetic characterization of the urethane-induced murine lung cell line LA-4 as a model for human squamous cell lung cancer
Document Type
Academic Journal
Author
Source
Molecular and Clinical Oncology. January 2022, Vol. 16 Issue 1
Subject
Language
English
ISSN
2049-9450
Abstract
Introduction Human lung malignancies are one of the leading causes of cancer-associated death and account for ~17% of annual new tumor diagnoses worldwide. Lung cancers are categorized into the following [...]
The murine tumor cell line LA-4 (also known as LA4 or LA 4) has been extensively used in ~70 studies from 1975 to present. However, the genetic characteristics have not been comprehensively delineated, apart from a single solid-stain cytogenetic study, which reported an average of 116 chromosomes per cell. LA-4 was created via urethane induction in an A/He mouse and demonstrated characteristic features of lung adenoma cells. In the present study, multicolor banding-based molecular cytogenetics was combined with molecular karyotyping to characterize ploidy, copy number alterations and chromosomal breakpoints of LA-4. A hyper-tetraploid karyotype with 85-93 chromosomes per cell, three distinct (pseudo-) dicentric derivatives, two neocentrics, four unbalanced translocations, two chromosomes with terminal deletions and one chromosome with a balanced inversion were detected. The results were translated into the human genome and a comparison with the literature revealed that LA-4 is well-suited as a murine model for human squamous cell lung cancer. Key words: lung cancer, adenoma, murine cell line LA-4, murine multicolor banding, array comparative genomic hybridization
The murine tumor cell line LA-4 (also known as LA4 or LA 4) has been extensively used in ~70 studies from 1975 to present. However, the genetic characteristics have not been comprehensively delineated, apart from a single solid-stain cytogenetic study, which reported an average of 116 chromosomes per cell. LA-4 was created via urethane induction in an A/He mouse and demonstrated characteristic features of lung adenoma cells. In the present study, multicolor banding-based molecular cytogenetics was combined with molecular karyotyping to characterize ploidy, copy number alterations and chromosomal breakpoints of LA-4. A hyper-tetraploid karyotype with 85-93 chromosomes per cell, three distinct (pseudo-) dicentric derivatives, two neocentrics, four unbalanced translocations, two chromosomes with terminal deletions and one chromosome with a balanced inversion were detected. The results were translated into the human genome and a comparison with the literature revealed that LA-4 is well-suited as a murine model for human squamous cell lung cancer. Key words: lung cancer, adenoma, murine cell line LA-4, murine multicolor banding, array comparative genomic hybridization