[HTML][HTML] Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha

I Conde, MVT Lobo, J Zamora, J Pérez, FJ González… - BMC cancer, 2008 - Springer
I Conde, MVT Lobo, J Zamora, J Pérez, FJ González, E Alba, B Fraile, R Paniagua…
BMC cancer, 2008Springer
Background 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 …
Background
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.
Methods
Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis.
Results
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.
Conclusion
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.
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