Aberrant Expression of p14 in Human Cancers: A New Biomarker?

The and genes are located on the locus, both showing tumor suppressive activity. ARF has been shown to monitor potentially harmful oncogenic signalings, making early stage cancer cells undergo senescence or programmed cell death to prevent cancer. Conversely, detects both aging and incipient cancer cell signals, and thus these two gene functions are different. The efficiency of detection of oncogenic signals is more efficient for the for the former than the latter in the mouse system. Both and genes are inactivated by gene deletion, promoter methylation, frame shift, aberrant splicing although point mutations for the coding region affect only the latter. Recent studies show the splicing alterations that affect only or both and genes suggesting that is inactivated in human tumors more frequently than what was previously thought. The gene is activated by E2Fs and Dmp1 transcription factors while it is repressed by Bmi1, Tbx2/3, Twist1, and Pokemon nuclear proteins. It is also regulated at protein levels by Arf ubiquitin ligase named ULF, MKRN1, and Siva1. The prognostic value of ARF overexpression is controversial since it is induced in early stage cancer cells to eliminate pre-malignant cells (better prognosis); however, it may also indicate that the tumor cells have mutant p53 associated with worse prognosis. The ARF tumor suppressive protein can be used as a biomarker to detect early stage cancer cells as well as advanced stage tumors with p53 inactivation.