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Molecular Biology and Genetics

Comparative Decreases in Tyrosinase, TRP-1, TRP-2, and Pmel 17/Silver Antigenic Proteins from Melanotic to Amelanotic Stages of Syngeneic Mouse Cutaneous Melanomas and Metastases

Seth J. Orlow, Willys K. Silvers, Bao-Kang Zhou and Beatrice Mintz
Seth J. Orlow
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Willys K. Silvers
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Bao-Kang Zhou
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Beatrice Mintz
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DOI:  Published April 1998
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Abstract

Malignant cutaneous melanomas and metastases were taken directly from in situ lesions of genetically identical (C57BL/6 strain) Tyr-SV40E transgenic mice, and samples were analyzed by Western immunoblotting with antisera specific for the COOH terminus of each of four melanocytic proteins. These were tyrosinase, TRP-1, TRP-2, and Pmel 17/silver. Of the 13 melanomas examined, there were 5 melanotic primary tumors, 5 amelanotic primary tumors, and 3 amelanotic metastases. The melanotic tumors expressed all of the markers to some extent. In contrast, the amelanotic tumors lacked detectable levels of one, two, or three of the proteins, except for an apparently amelanotic tumor sample in which all were expressed, but in which some melanotic cells were likely to have been present. Thus, despite some variability, there is clearly a downward trend in the presence of these proteins as the tumors become amelanotic, a pigmentary change associated with ongoing malignant progression. In the amelanotic tumors, tyrosinase was most often deficient, whereas TRP-2 was most often persistently expressed. These results, obtained from melanomas of syngeneic origin, indicate that tumors in the relatively early stages of malignancy might be more responsive than later-stage tumors to immunotherapy involving an ensemble of antigenic peptides of the tested gene products. Moreover, TRP-2 peptides may be especially useful for therapeutic intervention at the later stages.

Footnotes

  • ↵1 This work was supported by American Cancer Society Research Grant NP-917 (to B. M.), USPHS Grants CA-06927 and RR-05539 to the Fox Chase Cancer Center, and USPHS Grant AR-41880 and an Irma T. Hirschl Career Scientist Award (to S. J. O.).

  • ↵2 Visiting Scientist from the University of Pennsylvania, Philadelphia, PA 19104.

  • ↵3 To whom requests for reprints should be addressed, at Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111.

  • Received December 16, 1997.
  • Accepted February 2, 1998.
  • ©1998 American Association for Cancer Research.
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April 1998
Volume 58, Issue 7
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Comparative Decreases in Tyrosinase, TRP-1, TRP-2, and Pmel 17/Silver Antigenic Proteins from Melanotic to Amelanotic Stages of Syngeneic Mouse Cutaneous Melanomas and Metastases
Seth J. Orlow, Willys K. Silvers, Bao-Kang Zhou and Beatrice Mintz
Cancer Res April 1 1998 (58) (7) 1521-1523;

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Comparative Decreases in Tyrosinase, TRP-1, TRP-2, and Pmel 17/Silver Antigenic Proteins from Melanotic to Amelanotic Stages of Syngeneic Mouse Cutaneous Melanomas and Metastases
Seth J. Orlow, Willys K. Silvers, Bao-Kang Zhou and Beatrice Mintz
Cancer Res April 1 1998 (58) (7) 1521-1523;
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