CYP24A1 expression inversely correlates with melanoma progression: clinic-pathological studies.
CYP24A1 expression inversely correlates with melanoma progression: clinic-pathological studies.
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DOI：
10.3390/ijms151019000
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发表时间：
2014-10-20
影响因子：
5.6
通讯作者：
Slominski AT
中科院分区：
文献类型：
--
作者：
Brożyna AA;Jochymski C;Janjetovic Z;Jóźwicki W;Tuckey RC;Slominski AT
24-羟化酶（CYP24A1）的主要作用是维持1,25-二羟基维生素D3 （1,25(OH)2D3）的稳态。最近发现CYP24A1还能催化20(OH)D3的羟基化，产生具有非常有效的抗肿瘤活性的二羟基衍生物。先前我们发现维生素D受体（VDR）和CYP27B1表达与皮肤黑色素瘤的进展、侵袭性和总体或无病生存呈正相关。因此，我们分析了CYP24A1表达与痣、皮肤黑色素瘤和转移瘤的临床病理特征的关系。在黑色素细胞肿瘤中，CYP24A1水平高于正常表皮。CYP24A1平均水平在痣和早期黑色素瘤中最高。随着黑色素瘤的进展，CYP24A1水平下降，在晚期与正常表皮和转移相当。CYP24A1的表达与VDR、CYP27B1呈正相关，与有丝分裂活性呈负相关。较低的CYP24A1水平与溃疡、坏死、结节型和无色素表型的存在相关。此外，缺乏可检测的CYP24A1表达与较短的总生存期和无病生存期有关。总之，局部维生素D内分泌系统影响黑色素瘤的行为，在肿瘤发展的早期阶段，CYP24A1水平的升高似乎对黑素细胞痣的形成和黑色素瘤的发生或进展有重要影响。
The major role of 24-hydroxylase (CYP24A1) is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) homeostasis. Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OH)D3, producing dihydroxy-derivatives that show very effective antitumorigenic activities. Previously we showed a negative correlation of vitamin D receptor (VDR) and CYP27B1 expression with progression, aggressiveness and overall or disease-free survivals of skin melanomas. Therefore, we analyzed CYP24A1 expression in relation to clinicopathomorphological features of nevi, skin melanomas and metastases. In melanocytic tumors, the level of CYP24A1 was higher than in the normal epidermis. The statistically highest mean CYP24A1 level was found in nevi and early stage melanomas. With melanoma progression, CYP24A1 levels decreased and in advanced stages were comparable to the normal epidermis and metastases. Furthermore, the CYP24A1 expression positively correlated with VDR and CYP27B1, and negatively correlated with mitotic activity. Lower CYP24A1 levels correlated with the presence of ulceration, necrosis, nodular type and amelanotic phenotypes. Moreover, a lack of detectable CYP24A1 expression was related to shorter overall and disease-free survival. In conclusion, the local vitamin D endocrine system affects melanoma behavior and an elevated level of CYP24A1 appears to have an important impact on the formation of melanocytic nevi and melanomagenesis, or progression, at early stages of tumor development.
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影响因子：
8.8
作者：
Janjetovic, Z.;Brozyna, A. A.;Slominski, A. T.
通讯作者：
Slominski, A. T.
影响因子：
4.3
作者：
Kosa, Janos P.;Horvath, Peter;Lakatos, Peter
通讯作者：
Lakatos, Peter
影响因子：
4.3
作者：
Halaban R;Zhang W;Bacchiocchi A;Cheng E;Parisi F;Ariyan S;Krauthammer M;McCusker JP;Kluger Y;Sznol M
通讯作者：
Sznol M
DOI：
10.1016/j.ecl.2010.02.010
发表时间：
2010-06
影响因子：
4.5
作者：
Hewison, Martin
通讯作者：
Hewison, Martin
影响因子：
3.2
作者：
Horvath, Henrik C.;Lakatos, Peter;Kallay, Enikoe
通讯作者：
Kallay, Enikoe