Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM Swine Model
Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM Swine Model
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DOI：
10.1111/j.1755-148x.2008.00442.x
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发表时间：
2008-04-01
影响因子：
4.3
通讯作者：
Vincent-Naulleau, S.
中科院分区：
文献类型：
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作者：
Rambow, F.;Malek, O.;Vincent-Naulleau, S.
在皮肤黑色素瘤患者中观察到部分和少数完全自发消退的病例，但对所涉及的分子机制知之甚少。携带成黑色素细胞瘤的Libechov小型猪（MeLiM）是研究自发消退现象的合适动物模型，因为MeLiM猪表现出自然发生的黑色素瘤，其在出生后6个月完全消退。在这项研究中，我们使用抑制性消减杂交（SSH），以确定在猪黑色素瘤组织和黑色素瘤细胞培养的黑色素瘤消退的分子决定因素。参与细胞粘附，通讯，运动，信号转导，细胞增殖，运输和免疫反应的负调控的几个标志物被确定与黑色素瘤消退，而参与黑色素合成的主要基因表现出强烈的下调。对于最差异表达的基因，我们用qRT-PCR和免疫组织化学方法验证了SSH获得的结果（CD 9，MITF，RARRES 1）。最值得注意的是，在黑色素瘤中，我们首次确定了视黄酸应答基因1（RARRES 1）作为黑色素瘤消退过程的主要参与者。这是第一个在猪黑色素瘤消退中进行的基因表达研究，可能有助于为人类黑色素瘤治疗寻找新的治疗靶点。
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.