Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma

• Published in: Scientific reports Vol. 5; no. 1; p. 14068
• Main Authors: Anne Conti, Mary, Saleh, Anthony D., Brinster, Lauren R., Cheng, Hui, Chen, Zhong, Cornelius, Shaleeka, Liu, Chengyu, Ma, Xuefei, Van Waes, Carter, Adelstein, Robert S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-09-2015; Nature Publishing Group
• Subjects: 631/67/68; 631/67/70; Animals; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Cell Movement - genetics; Cell Transformation, Neoplastic - genetics; Clonal deletion; Disease Models, Animal; Disease Progression; Epithelium; Gene Deletion; Gene Expression; Genetic Variation; Genotype; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Heart diseases; Humanities and Social Sciences; Humans; Invasiveness; Mice; Mice, Knockout; Mucous Membrane - metabolism; Mucous Membrane - pathology; multidisciplinary; Myosin; Neoplasm Grading; Neoplasm Invasiveness; Nkx2.5 protein; Nonmuscle Myosin Type IIA - genetics; Oncogene Protein p21(ras) - genetics; Oncogene Protein p21(ras) - metabolism; p53 Protein; Phenotype; Recombinase; Reproducibility of Results; Science; Squamous cell carcinoma; Stem cells; Tongue; Tongue Neoplasms - genetics; Tongue Neoplasms - pathology; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep14068

To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (A
Nkx
/A
Nkx
) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 A
Nkx
/A
Nkx
) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from a different embryonic stem cell clone was tested. This second line also develops SCC indistinguishable from the first (15/15). In A
Nkx
/A
Nkx
mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis.