Yang Guang, Thieu Khanh, Tsai Kenneth Y, Piris Adriano, Udayakumar Durga, Njauw Ching-Ni Jenny, Ramoni Marco F, Tsao Hensin
Wellman Center for Photomedicine, Massachusetts General Hospital Boston, Massachusetts 02114-2696, USA.
Cancer Res. 2009 Dec 1;69(23):9029-37. doi: 10.1158/0008-5472.CAN-09-0783. Epub 2009 Nov 10.
Like all primary cells in vitro, normal human melanocytes exhibit a physiologic decay in proliferative potential as it transitions to a growth-arrested state. The underlying transcriptional program(s) that regulate this phenotypic change is largely unknown. To identify molecular determinants of this process, we performed a Bayesian-based dynamic gene expression analysis on primary melanocytes undergoing proliferative arrest. This analysis revealed several related clusters whose expression behavior correlated with the melanocyte growth kinetics; we designated these clusters the melanocyte growth arrest program (MGAP). These MGAP genes were preferentially represented in benign melanocytic nevi over melanomas and selectively mapped to the hepatocyte fibrosis pathway. This transcriptional relationship between melanocyte growth stasis, nevus biology, and fibrogenic signaling was further validated in vivo by the demonstration of strong pericellular collagen deposition within benign nevi but not melanomas. Taken together, our study provides a novel view of fibroplasia in both melanocyte biology and nevogenesis.
与体外培养的所有原代细胞一样，正常人黑素细胞在向生长停滞状态转变时，其增殖潜能会出现生理性衰退。调节这种表型变化的潜在转录程序在很大程度上尚不清楚。为了确定这一过程的分子决定因素，我们对处于增殖停滞状态的原代黑素细胞进行了基于贝叶斯的动态基因表达分析。该分析揭示了几个相关的簇，其表达行为与黑素细胞生长动力学相关；我们将这些簇命名为黑素细胞生长停滞程序（MGAP）。这些MGAP基因在良性黑素细胞痣中比在黑色素瘤中更具代表性，并选择性地映射到肝纤维化途径。黑素细胞生长停滞、痣生物学和纤维化信号之间的这种转录关系在体内通过良性痣而非黑色素瘤中强烈的细胞周胶原沉积得到进一步验证。综上所述，我们的研究为黑素细胞生物学和痣形成中的纤维增生提供了新的视角。
