Multidrug Resistance and Apoptosis in Oral Squamous Carcinoma Cells : Role of Transcription Factors
Departmental Bulletin Paper
Transcription factors are key factors of a number of cellular processes, such as cell growth, carcinogenesis, and apoptosis. Tumor cells including squamous carcinoma cells initially respond to chemotherapeutic drugs, however, they often acquire anti-apoptotic property and drug resistance. Human oral squamous carcinoma cell line SCCTF cells were isolated as minimal sensitivity to a variety of anticancer drugs, whereas SCCKN cells were isolated as highly sensitive to these reagents. We have clarified the molecular mechanisms that regulate apoptosis and the multidrug resistance using these cell lines. SCCTF cells expressed some transcription factors including EGR-1, NF-Y, and NF-kB. Okadaic acid and calyculin A, inhibitors of protein phosphatases type 1 and 2A, decreased EGR-1 expression and induced apoptosis in SCCKN cells. In contrast, these inhibitors stimulated the phosphorylation of EGR-1 protein in SCCTF cells during apoptosis. Activation of EGR-1 was involved in the up-regulation of PTEN, which in turn decreased phosphorylation level of AKT in SCCTF cells. Moreover, multidrug resistance-1 (MDR1) gene was expressed higher level in SCCTF cells. Inhibition of MDR1 promoted anticancer drug-induced apoptosis. NF-Y and its binding sites were demonstrated to play an important role in transcriptional regulation of MDR1 in SCCTF cells. In this review, we focus on the roles of transcription factors in MDR1 expression and apoptosis in oral squamous carcinoma cells through our recent studies.
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