The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells.

Abstract

Differential gene expression of cell lines derived from a malignant melanoma or its autologous lymph node metastasis using cDNA arrays indicated down-regulation of PRSS11, a gene encoding the serine protease HtrA1, a homolog of the Escherichia coli protease HtrA, in the metastatic line. Stable PRSS11 overexpression in the metastatic cell line strongly inhibited proliferation, chemoinvasion and Nm23-H1 protein expression in vitro, as well as cell growth in vivo in nu/nu mice. A polyclonal anti-HtrA1 serum demonstrated a significantly higher expression in primary melanomas when compared to unrelated metastatic lesions in a human melanoma tissue array, and down-modulation of HtrA1 expression in autologous lymph node melanoma metastases in seven out of 11 cases examined. These results suggest that down-regulation of PRSS11 and HtrA1 expression may represent an indicator of melanoma progression.

• Authors: Alfonso Baldi, Antonio De Luca, Monica Morini, Tullio Battista, Armando Felsani, Feliciano Baldi, Caterina Catricalà, Ada Amantea, Douglas M Noonan, Adriana Albini, Pier Giorgio Natali, Daniela Lombardi, Marco G Paggi
• Journal: Oncogene (Oncogene) Vol. 21 Issue 43 Pg. 6684-8 (Sep 26 2002) ISSN: 0950-9232 [Print] England
• PMID: 12242667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serine Endopeptidases

Topics

• Animals
• Chromosome Mapping
• Down-Regulation
• Gene Expression Regulation, Enzymologic
• Humans
• Immunohistochemistry
• Melanoma (enzymology, pathology, secondary)
• Rabbits
• Serine Endopeptidases (analysis, genetics)