Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy

胆碱激酶 磷酸胆碱 生物 癌变 胆碱 乳腺癌 癌症研究 体内 癌症 内科学 内分泌学 生物化学 医学 遗传学 磷脂 磷脂酰胆碱
作者
Ana Ramı́rez de Molina,Ruth Gutiérrez,Maria Angeles Ramos,José María Silva,Javier Silva,Félix Bonilla,José Javier Sánchez,Juan Carlos Lacal
出处
期刊:Oncogene [Springer Nature]
卷期号:21 (27): 4317-4322 被引量:241
标识
DOI:10.1038/sj.onc.1205556
摘要

Choline kinase (ChoK) and its product, phosphocholine (PCho), have been implicated in human carcinogenesis. Inhibition of this enzyme has been shown to be an efficient antitumor strategy in vivo. The aim of this study was to assess the relationship between the regulation of ChoK and clinical features in patients with breast cancer. To that end, normal and tumoral tissues from 53 patients with breast carcinomas were analysed for ChoK activity and expression, and compared to some clinical parameters. We report a relevant increase in ChoK activity in 38.5% of the tumoral tissues analysed when compared to the normal levels in healthy tissues. Furthermore, some clinical features were found significant versus ChoK status. First, an association of choline enzymatic activity with histological tumor grade was observed (P<0.001). In addition, increased ChoK activity was also associated with ER-negative breast carcinomas (P=0.037). A significant association between ChoK overexpression and both high histologic tumor grade (P=0.017) and ER-negative tumors (P=0.003) was found. Finally, ChoK overexpression was found in 17% of the samples and all corresponded with those that display the highest increase in ChoK activity (P<0.001). Here we provide evidence that ChoK may be related to the development of human breast cancer, suggesting that this finding may constitute the basis for the development of a novel antitumoral strategy for these patients.
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