Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression.

Abstract

Cutaneous melanomas of Tyr-SV40E transgenic mice (mice whose transgene consists of the tyrosinase promotor fused to the coding regions of simian virus 40 early genes) strikingly resemble human melanomas in their development and progression. Unlike human melanomas, the mouse tumors all arise in genetically identical individuals, thereby better enabling expression of specific genes to be characterized in relation to advancing malignancy. The products of pigment genes are of particular interest because peptides derived from these proteins have been reported to function as autoantigens with immunotherapeutic potential in some melanoma patients. However, the diminished pigmentation characteristic of many advanced melanomas raises the possibility that some of the relevant products may no longer be expressed in the most malignant cells. We have therefore investigated the contributions of several pigment genes in melanotic vs. relatively amelanotic components of primary and metastatic mouse melanomas. The analyses reveal marked differences within and among tumors in levels of mRNAs and proteins encoded by the wild-type alleles at the albino, brown, slaty, and silver loci. Tyrosinase (the protein encoded by the albino locus) was most often either absent or undetectable as melanization declined. The protein encoded by the slaty locus (tyrosinase-related protein 2) was the only one of those tested that was clearly present in all the tumor samples. These results suggest that sole reliance on targeting tyrosinase-based antigens might selectively favor survival of more malignant cells, whereas targeting the ensemble of the antigens tested might contribute toward a more inclusive and effective antimelanoma strategy.

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

“…These include various tissues of the central nervous system such as substantia nigra, forebrain and midbrain, as well as melanocytes and melanoma cells (Orlow et al, 1995;Bernd et al, 1994;Tief et al, 1998). Since cancer cells can often ectopically express genes that are characteristic of other cell lineages, we examined a panel of non-melanoma human cancer cell lines for the expression of TYRP2.…”

Comparison of Tyrosinase-related Protein-2, S-100, and Melan A Immunoreactivity in Canine Amelanotic Melanomas

“…10,11 Several enzymes that participate in melanogenesis, including tyrosinase, tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), and Pmel17/Silver, are expressed in pigmented melanomas. 7,8,13 Although many of these melanogenic enzymes are absent from amelanotic melanomas, TRP-2 (DOPAchrome tautomerase) appears to be retained in many unpigmented melanomas. 7,8 In fact, recent studies have suggested that TRP-2 may be a good candidate for immunotherapy of amelanotic melanoma.…”

“…7,8,13 Although many of these melanogenic enzymes are absent from amelanotic melanomas, TRP-2 (DOPAchrome tautomerase) appears to be retained in many unpigmented melanomas. 7,8 In fact, recent studies have suggested that TRP-2 may be a good candidate for immunotherapy of amelanotic melanoma. 7,8 In the mouse, TRP-2 is encoded by the slaty locus.…”

“…7,8 In fact, recent studies have suggested that TRP-2 may be a good candidate for immunotherapy of amelanotic melanoma. 7,8 In the mouse, TRP-2 is encoded by the slaty locus. The enzyme catalyzes the rearrangement of DOPAchrome to the carboxylated derivative DHICA (5,6-dihydroxyindole-2-carboxylic acid).…”

“…Loss of pigmentation in melanomas may be associated with malignancy; 2,7,8 thus, it is important to identify amelanotic melanomas and to distinguish them from other tumor types. Immunohistochemistry for S-100 is widely used to confirm the diagnosis of amelanotic melanoma in humans and animals.…”