Doxycycline-induced exogenous Bmi-1 expression enhances tumor formation in a murine model of oral squamous cell carcinoma.

Doxycycline-induced exogenous Bmi-1 expression enhances tumor formation in a murine model of oral squamous cell carcinoma.
Cancer Biol Ther. 2020 Feb 09;:1-12
Authors: Kalish JM, Tang XH, Scognamiglio T, Zhang T, Gudas LJ
Abstract
B Cell-Specific Moloney Murine Leukemia Virus Integration Site 1 (Bmi-1, Bmi1), an epigenetic protein, is necessary for normal stem cell self-renewal in adult animals and for cancer stem cell (CSC) functions in adult animals. To elucidate the functions of Bmi-1 in the oral cavity we created a transgenic mouse line (KrTBmi-1) that expresses ectopic, Flag-tagged Bmi-1 in tongue basal epithelial stem cells only upon doxycycline (DOX) treatment. Genome wide transcriptomics and Ingenuity Pathway Analysis identified several pathways altered by exogenous Bmi-1 expression in the normal tongue epithelium, including EIF2 signaling (P value = 1.58 x 10-49), mTOR signaling (P value = 2.45 x 10-12), oxidative phosphorylation (P = 6.61 x 10-3) and glutathione redox reactions I (P = 1.74 x 10-2). Overall, our data indicate that ectopic Bmi-1 expression has an impact on normal tongue epithelial homeostasis. We then assessed the KrTBmi-1 mice in the 4-nitroquinoline 1-oxide (4-NQO) model of oral carcinogenesis. We found that 80% of mice expressing exogenous Bmi-1 (+DOX, +4-NQO KrTBmi-1; N = 10) developed tumors classified as grade 3 or higher, compared to 60% and 40% of mice expressing just endogenous Bmi-1 (+DOX, +4...

Source: Cancer Biology and Therapy - February 8, 2020 Category: Cancer & Oncology Authors: Kalish JM, Tang XH, Scognamiglio T, Zhang T, Gudas LJ Tags: Cancer Biol Ther Source Type: research