Ferritin light chain down-modulation generates depigmentation in human metastatic melanoma cells by influencing tyrosinase maturation.

Abstract:

:Recently, after the identification of ferritin light chain (L-ferritin) gene and protein over-expression in human metastatic melanoma cells, we engineered, starting from the LM metastatic melanoma cell line, clones in which L-ferritin gene expression was down-regulated by the stable expression of a specific antisense construct. The present investigation started from the observation that L-ferritin down-regulated LM cells displayed a less pigmented phenotype, confirmed by a major decrease of total melanin, when compared to control LM cells. This finding was accompanied by a dramatic decrease in tyrosinase activity, which was not paralleled by a concomitant reduction of the amount of tyrosinase specific mRNA. Western blot analysis of tyrosinase in control LM cells displayed a pattern, which corresponds to the progressive glycosylation of the native protein up to the 80 kDa form, considered the functional one. Tyrosinase pattern assayed in L-ferritin down-regulated LM cells showed the remarkable absence of the 80 kDa form and a prevalence of endoglycosidase H (endo H)-sensitive immature (70 kDa) tyrosinase, accumulated in the endoplasmic reticulum (ER), as confirmed by confocal microscopy analysis. These results demonstrate that, in a human metastatic melanoma cell line, the stress condition promoted by L-ferritin down-modulation, can substantially influence proper maturation of tyrosinase.

journal_name

J Cell Physiol

authors

Maresca V,Flori E,Cardinali G,Briganti S,Lombardi D,Mileo AM,Paggi MG,Picardo M

doi

10.1002/jcp.20543

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

843-8

issue

3

eissn

0021-9541

issn

1097-4652

journal_volume

206

pub_type

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