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Molecular identification, localization and function of platelet-type 12-lipoxygenase in human melanoma progression, under experimental and clinical conditions.
- Source :
-
Melanoma research [Melanoma Res] 2004 Aug; Vol. 14 (4), pp. 245-50. - Publication Year :
- 2004
-
Abstract
- As previous studies suggested the expression of a 12-LOX enzyme in murine and human melanoma cell lines, the primary aim of this project was to genetically identify the 12-LOX enzyme (platelet-, leukocyte- or epithelial form). By using reverse transcriptase-polymerase chain reaction, sequencing and various immunological techniques we have demonstrated conclusively the expression of the platelet-type 12-LOX in human melanoma cells of different origin, in their transplanted xenografts and in fresh human skin tumors. Furthermore, we found that p12-LOX is able to provide a survival signal for melanoma cells since inhibition of the enzyme by general LOX or selective 12-LOX inhibitors induced apoptosis in vitro. p12-LOX of human melanoma has been shown to be involved in the control of the metastatic phenotype, since we have detected the upregulation of the 12-LOX protein expression in spontaneously metastasizing xenografts and in thick human skin tumors (> 3.0 mm) characterized by high risk for the development of metastasis. Co-expression of two megakaryocytic genes, p12-LOX and alphaIIb integrin chains, was found to be a frequent phenomenon in human melanoma (approximately 70%) suggesting a common regulatory defect in this tumor.<br /> (Copyright 2004 Lippincott Williams & Wilkins)
- Subjects :
- Animals
Apoptosis drug effects
Arachidonate 12-Lipoxygenase genetics
Cell Line, Tumor
Disease Progression
Enzyme Inhibitors pharmacology
Humans
Immunohistochemistry
Integrins
Melanoma genetics
Mice
Microscopy, Confocal
Neoplasm Metastasis pathology
Neoplasm Transplantation
Platelet Membrane Glycoprotein IIb genetics
Platelet Membrane Glycoprotein IIb metabolism
Rats
Skin Neoplasms metabolism
Skin Neoplasms pathology
Transplantation, Heterologous pathology
Arachidonate 12-Lipoxygenase metabolism
Blood Platelets enzymology
Melanoma enzymology
Melanoma pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0960-8931
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Melanoma research
- Publication Type :
- Academic Journal
- Accession number :
- 15305153
- Full Text :
- https://doi.org/10.1097/01.cmr.0000138479.00897.d8