Conde Isabel, Lobo María V T, Zamora Javier, Pérez Julio, González Francisco J, Alba Emilio, Fraile Benito, Paniagua Ricardo, Arenas María I
Department of Cell Biology and Genetics, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
BMC Cancer. 2008 Jun 19;8:174. doi: 10.1186/1471-2407-8-174.
The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P-450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to determine whether their expression profile in localized infiltrative breast cancer is associated with an increased risk of recurrent disease.
Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis.
Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha.
Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator.
人孕烷X受体（hPXR）是一种孤儿核受体，可诱导类固醇诱导的细胞色素P-450基因启动子中存在的反应元件转录。这种激活需要视黄酸X受体（RXRs）的参与，RXRs是hPXR形成异二聚体所需的伙伴。我们研究了hPXR和RXRs在正常、癌前和恶性乳腺组织中的表达，以确定它们在局限性浸润性乳腺癌中的表达谱是否与疾病复发风险增加相关。
对99例患者的乳腺样本进行处理，包括良性乳腺疾病、原位癌和浸润性癌，进行免疫组织化学和蛋白质印迹分析。
出现复发疾病的患者的癌细胞显示两种hPXR亚型均有较高的细胞质定位。只有在48个月前复发的浸润性癌显示hPXR亚型2的核定位。这种定位与RXR-α的核免疫表达相关。
乳腺癌细胞可以表达hPXR的1型和2型变体。复发的浸润性癌显示hPXR和RXR-α均有核定位；因此，hPXR的过表达和亚细胞定位变化可被视为一种潜在的新的预后指标。
