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Journal Articles Oncogene Year : 2006

Expression of cathepsin L in human tumor cells is under the control of distinct regulatory mechanisms

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Abstract

Cathepsin L, a cysteine protease, is overexpressed in human tumor cells and plays a major role in melanoma progression. Our aim was herein to identify molecular mechanisms, which contribute to its overexpression. We found that cathepsin L protein expression correlated with mRNA level in tumor cells. Therefore, we focused on mechanisms involved in cathepsin L mRNA regulation. CpG island was localized in the 5' region of cathepsin L gene that encompassed regulatory regions identified as essential for promoter activity. CpG dinucleotides, not methylated in any melanoma cells analysed, were methylated in a B lymphoma cell line, which poorly express cathepsin L. Our data demonstrate that in lymphoma cells, cathepsin L silencing was methylation-dependent. Furthermore, gene amplification was involved in cathepsin L overexpression in one melanoma cell line, while transcriptional mechanisms but not mRNA stability are responsible of cathepsin L overexpression in others melanoma cells. In addition, NF-Y, Sp1, Sp2 and Sp3 transcription factors, essential to basal cathepsin L transcription, are not directly involved in overexpression. Thus, our data provides the first demonstration that cathepsin L expression in tumor cells is under the control of distinct molecular mechanisms.
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inserm-03738140 , version 1 (25-07-2022)

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Didier Jean, N Rousselet, R Frade. Expression of cathepsin L in human tumor cells is under the control of distinct regulatory mechanisms. Oncogene, 2006, 25 (10), pp.1474-1484. ⟨10.1038/sj.onc.1209196⟩. ⟨inserm-03738140⟩

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