Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM Swine Model

Pigment Cell and Melanoma Research - Tập 21 Số 2 - Trang 147-161 - 2008
Florian Rambow1,2,3, Olaf Malek1,2,3,4, Claudine Geffrotin2,3, Jean Jacques Leplat2,3, Stéphan Bouet2,3, Guillaume Piton2,3, Karine Hugot5, Claudia Bevilacqua6, Vratislav Horák4, Vincent Coustham2,3
1Both authors contributed equally to this work
2CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d'Etude du Génome, Jouy-en-Josas, F-78352, France
3INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
4Institute of Animal Physiology and Genetics, 27721 Libechov, Czech Republic
5INRA, DGA, Centre de Ressources Biologiques Gadie, Jouy-en-Josas, F-78352 France
6INRA, DGA, Plateau d’instrumentation et de compétences en transcriptomique, Jouy-en-Josas, F-78352 France

Tóm tắt

Summary

Partial and some few cases of complete spontaneous regression have been observed in cutaneous melanoma patients but little is known about the molecular mechanisms involved. The Melanoblastoma‐bearing Libechov Minipig (MeLiM) is a suitable animal model to study the phenomenon of spontaneous regression because MeLiM pigs exhibit naturally occurring melanomas which regress completely 6 months after birth. In this study, we used suppression subtractive hybridization (SSH) to identify molecular determinants of melanoma regression within swine melanoma tissues and melanoma cell cultures. Several markers involved in cell‐adhesion, ‐communication, ‐motility, signal transduction, negative regulation of cell proliferation, transport and immune response were identified that correlated with melanoma regression whereas the main genes involved in melanin synthesis showed a strong downregulation. For the most differentially expressed genes, we validated the results obtained by SSH with qRT‐PCR and with immunohistochemistry for some of them (CD9, MITF, RARRES1). Most notable, for the first time in melanoma, we identified the retinoic acid responder 1 gene (RARRES1) as a main actor of the regression process in melanoma. This first gene expression study in swine melanoma regression, may contribute to the finding of new therapeutic targets for human melanoma treatment.

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Pigment Cell and Melanoma Research

Tập 21 Số 2

147-161

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