Pax9 mediated cell survival in oral squamous carcinoma cell enhanced by c‐myb

Abstract

Paired box gene 9 (Pax9) and c-myb are transcription factors that regulate the expression of the genes involved in mediating cell proliferation, resistance to apoptosis, and migration. However, the function of Pax9 in oral squamous cell carcinoma (OSCC) is virtually unknown. This study examined the anti-apoptotic roles of Pax9 and c-myb, and clarified interaction between the two genes in KB cells. Inhibition of Pax9 caused the induction of apoptosis with enhanced cleavage of caspase-3 and PARP, accelerated Bax, and reduced Bcl-2 expression. Transducing c-myb cells with adenovirus c-myb (Ad/c-myb) were induced cell growth and inhibited apoptosis, but dominant-negative myb cells (Ad/DN-myb) were not affected. Pax9 was upregulated in the Ad/c-myb cells with simultaneous decrease in the Ad/DN-myb infection. However, c-myb remained unaffected in the Pax9 small interfering RNA (siRNA) transfected cells. Moreover, the Pax9 siRNA transfected cells and Ad/DN-myb infected cells were able to arrest the cell cycle at the G(0) phase. This suggests that Pax9 and c-myb expression in KB cells is essential for cell growth, and survival is enhanced by c-myb. Disrupting the function of c-myb and Pax9 could be a potential target for cancer treatment.

Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia

“…PAX9 is one of the nine members of "paired box” ( PAX )-containing transcription factor family and its inhibition has been shown to induce apoptosis with increased cleavage of caspase-3 and PARP , increased expression of BAX and decreased expression of BCL-2 in oral squamous cell carcinoma [53]. In the recent years, it has emerged as one of the biomarkers of cell proliferation in lung cancer [54].…”

“…This explanation is further supported by progressively increasing gene expression levels of PAX9 and CRY1 in coherence with advanced Rai stage and higher IPI scores. The mechanism(s) underlying such an influence of these two genes in CLL pathogenesis are not known but might involve apoptotic [53, 55–57], or analogous pathways involved in cancer.…”

Prognostic value of PAX9 in patients with esophageal squamous cell carcinoma and its prediction value to radiation sensitivity

“…For example, Lee et al revealed that PAX9 inhibition causes the induction of apoptosis with enhanced cleavage of caspase-3 and poly ADP-ribose polymerase, increased expression levels of Bax and reduced expression levels of Bcl-2 in oral squamous cell carcinoma. In addition, cells transfected with PAX9 siRNA and cells infected with adenovirus-mediated expression of dominant-negative c-myb have been reported to display cell cycle arrest at the G 0 phase (30). The findings of the present study may support this mechanism.…”

“…As a transcription factor expressed in the tooth mesenchyme during tooth morphogenesis, heterozygous mutations in PAX9 have been associated with non-syndromic tooth agenesis, predominantly in the molars (25–28). In the last decade, the abnormal expression of the PAX9 gene, which is associated with the tumorigenesis, development, invasion and metastasis of many types of cancer, was observed in a variety of malignant human tumors (29,30). However, the expression level and prognostic value of PAX9 in malignant tumor cells remain inconclusive.…”

Apoptosis-inducing activity and tumor-specificity of antitumor agents against oral squamous cell carcinoma

“…Pax9 and c-myb expressions in KB cells seem to be essential for cell growth, and survival was enhanced by c-myb. Disruption of the function of c-myb and Pax9 induced G0 arrest [75].…”