Changes of PI3K/AKT/BCL2 signaling proteins in congenital Giant Nevi: melanocytes contribute to their increased survival and integrity

被引:13
作者
Drukker, Lior [1 ]
Margulis, Alexander [2 ]
Chaouat, Malka [1 ]
Levitzki, Rubina [1 ]
Maiorenko, Elena [1 ]
Ben Bassat, Hannah [1 ]
机构
[1] Hadassah Hebrew Univ, Med Ctr, Israel Natl Skin Bank Lab Expt Surg, Hadassah Med Ctr, IL-91120 Jerusalem, Israel
[2] Hadassah Hebrew Univ, Med Ctr, Hadassah Med Ctr, IL-91120 Jerusalem, Israel
关键词
Apoptosis; cell growth; CGN; melanocytes; PI3K/AKT/BCL2; signaling pathways; BETA-CATENIN; MOLECULAR PATHOGENESIS; BCL-XL; MELANOMA; APOPTOSIS; EXPRESSION; NOTCH1; AKT; PROGRESSION; KINASE;
D O I
10.3109/10799893.2013.838785
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Congenital Giant Nevi (CGN) are rare melanocytic lesions with the potential to regress into malignant melanoma. Simultaneous up-regulation and cooperative interactions of signaling pathways are crucial events in the pathogenesis of melanocytes. Our study aimed to identify changes in the expression and activation of proteins controlling survival and/or apoptosis of the key signaling pathways PI3K/AKT/BCL2 and Wnt/beta-catenin of CGN melanocytes. We applied a model of cultured melanocytes from paired CGN and normal appearing skin, and Western blot (WB) analyzed the expression and activation profile of survival and anti-apoptotic proteins of these signaling pathways, growth pattern, cell cycle and apoptosis. WB analysis demonstrated a significant higher expression level of activated AKT and of BCL2 proteins in the CGN melanocytes compared with paired melanocytes from normal appearing skin. A relative increase in the level of GSK3 and FOXO1 proteins, down stream targets of AKT, as well as of p beta-catenin was also detected in the CGN melanocytes compared with the controls. These changes were not affected by growth of the CGN melanocytes in reduced serum (starvation). Both cell populations shared a similar growth pattern, with no significant differences in the proportion of apoptotic cells and in cell cycle fractions. These data demonstrate for the first time, changes in signaling proteins of cultured CGN melanocytes. Further, suggesting that the changes in AKT/BCL2 signaling molecules might mediate growth and anti-apoptosis processes at least in part, thus increasing the survival potential of CGN melanocytes and maintaining their integrity.
引用
收藏
页码:359 / 366
页数:8
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