Correlation of p53, MDM2 and p14ARF protein expression in human esophageal squamous cell carcinoma

Abstract

Expression of p53 protein correlates with increased MDM2 and p14(ARF) protein levels in ESCC. In addition, status of p53 (wild-type versus mutant) rather than expression level of p53, MDM2, or p14(ARF) is likely to be the more critical determinant of clinical outcome.

Bidirectional Functions of Arsenic as a Carcinogen and an Anti-Cancer Agent in Human Squamous Cell Carcinoma

“…This is the first time we showed that there is a possibility in cooperation between MT1-MMP and p14ARF in cancer development in HSC5 cells. In the other hand, our results showed that 3 µM arsenic induced apoptosis of HSC5 cells via downregulation of N-cadherin (Figure 4A), which plays role in cell differentiation, transformation, as well as invasion [33]–[36] and upregulation p21(WAF1/CIP1) (Figure 4B), a tumor suppressor [20]–[24] at both transcript and expression levels. Our results in accordance with previous studies [37], [38] suggested that N-cadherin might participate to the associated-cell cycle arrest through the nuclear accumulation of cyclin-dependent kinase inhibitors p21.…”

“…Treatment with 3 µM of arsenic induced transcript and expression levels of MT1-MMP (Figure 3A-B) and inhibited transcript and expression levels of p14ARF (Figure 3C-D). Previous studies [20]–[24], [27] indicated that MT1-MMP and p14ARF might play important roles in modulating growth and invasion of squamous cell carcinoma cells. In accordance with these previous reports [20]–[24], [27], our results suggested that arsenic might promote invasion of HSC5 cells via upregulation of MT1-MMP and downregulation of p14ARF.…”

“…Treatment with 3 µM of arsenic strongly reduced transcript and expression levels of N-cadherin (Figure 4A-B) and promoted transcript and expression levels of p21(WAF1/CIP1) (Figure 4C-D). Previous studies [20]–[24], [29]–[36] showed that N-cadherin and p21(WAF1/CIP1) might play important roles in modulating of apoptosis of human squamous cell carcinoma cells. Our results in this study suggested that arsenic might cause apoptosis of HSC5 cells through downregulation of N-cadherin and/or upregulation of p21(WAF1/CIP1).…”

“…We then investigated the molecular mechanisms related to these events in HSC5 cells. Our results revealed that 3 µM arsenic enhanced cellular invasion through upregulation of membrane type 1 matrix metalloproteinase (MT1-MMP) (Figure 3A), which plays crucial roles in tumorigenesis [7], and downregulation of p14ARF (Figure 3B), which is an inhibitor for cell proliferation [20]–[24] at both transcript and expression levels. This is the first time we showed that there is a possibility in cooperation between MT1-MMP and p14ARF in cancer development in HSC5 cells.…”

“…p21(WAF1/CIP1) and p14ARF play important roles in controlling the cell cycle arrest by regulating the activity of cyclins and cyclin-dependent kinases (CDK) [16]–[19]. p21(WAF1/CIP1) and p14ARF are able to inhibit cell growth through cell cycle arrest of skin cancer cells including melanoma, squamous cell carcinoma and basal cell carcinoma [20]–[24]. Other reports revealed that exposure to arsenic cause cell transformation through the inhibition of both protein and gene expression of the tumor suppressors p19ARF [22]–[24].…”