PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
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DOI：
10.1371/journal.pone.0009977
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发表时间：
2010-04-22
期刊：
影响因子：
3.7
通讯作者：
Ziman M
中科院分区：
文献类型：
--
作者：
Medic S;Ziman M
皮肤恶性黑色素瘤是皮肤癌的一种侵袭性形式，产生于皮肤黑素细胞。转录因子PAX 3在发育过程中调节神经嵴细胞的黑素细胞特化，但在分化的黑素细胞中的表达是不确定的。相比之下，它经常在黑色素瘤和痣中发现，并且是黑色素瘤分期和检测的标志物。在这项研究中，我们分析了PAX 3在黑素细胞谱中的表达，从正常黑素细胞到良性和恶性病变细胞，以更好地评估其在这些不同组织中的功能。Pax 3和PAX 3（斜体）分别指小鼠和人基因;而Pax 3和PAX 3（非斜体）指相应的小鼠和人蛋白。通过免疫组织化学和qRT-PCR分析PAX 3表达。免疫荧光用于与分化、迁移和存活标志物的共表达。正如预期的那样，在痣和黑素瘤细胞中观察到PAX 3表达。在正常皮肤的黑素细胞中也发现了它，其中它与黑素细胞标记物MITF和MLANA共表达。与其下游靶标抗凋亡因子BCL 2L 1的共表达证实PAX 3是细胞存活调节剂。PAX 3还与黑素瘤细胞迁移标记物MCAM在真皮痣和黑素瘤细胞巢中共表达，但PAX 3的下游靶点不存在于正常表皮黑素细胞中，表明PAX 3在正常表皮黑素细胞和黑素瘤细胞中的不同作用。最有趣的是，正常皮肤中PAX 3阳性表皮黑素细胞的比例显示出HES 1和Ki 67共表达，表明其分化程度较低的增殖表型。我们的研究结果表明，PAX 3以前确定的作用，即调节未分化的塑料状态，可能在正常皮肤的黑素细胞中起作用。这种作用可能是细胞对环境刺激的反应所必需的，可能有助于PAX 3表达突出的黑素细胞病变的形成和发展。
Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanoma staging and detection. In this study we analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions to better assess its function in these various tissues. Pax3 and PAX3 (italicized) refer to the mouse and human gene, respectively; whereas Pax3 and PAX3 (non-italicized) refer to the corresponding mouse and human protein. PAX3 expression was analysed by immunohistochemistry and qRT-PCR. Immunofluorescence was used for co-expression with differentiation, migration and survival markers. As expected PAX3 expression was observed in naevi and melanoma cells. It was also found in melanocytes of normal skin where it co-expressed with melanocyte markers, MITF and MLANA. Co-expression with its downstream target, antiapoptotic factor BCL2L1 confirms PAX3 as a cell survival regulator. PAX3 was also co-expressed with melanoma cell migration marker MCAM in dermal naevi and melanoma cell nests, but this downstream target of PAX3 was not present in normal epidermal melanocytes, suggesting differential roles for PAX3 in normal epidermal melanocytes and melanoma cells. Most interestingly, a proportion of PAX3-positive epidermal melanocytes in normal skin show HES1 and Ki67 co-expression, indicating their less differentiated proliferative phenotype. Our results suggest that a previously identified role for PAX3, that of regulator of an undifferentiated plastic state, may operate in melanocytes of normal skin. This role, possibly required for cellular response to environmental stimuli, may contribute to formation and development of melanocytic lesions in which PAX3 expression is prominent.
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DOI：
10.1073/pnas.93.9.4213
发表时间：
1996-04-30
影响因子：
11.1
作者：
Epstein, JA;Shapiro, DN;Maas, RL
通讯作者：
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