DC-SCRIPT may have prognostic value in breast cancer
MedWire News: Dendritic cell-specific transcript (DC-SCRIPT) is a key regulator of nuclear receptor activity that may have prognostic value in breast cancer, according to researchers from The Netherlands. Nuclear receptors, including estrogen receptor (ER), progesterone receptor (PR)-B, peroxisome proliferator-activated receptor gamma (PPARγ), and retinoic acid receptor alpha (RARα) may contribute to the development and progression of breast cancer, but it is unclear how they are regulated, say Gosse Adema (Radboud University, Nijmegen) and colleagues.
In this study, Adema and team investigated the role of the novel transcriptional repressor DC-SCRIPT as co-regulator of these nuclear receptors and as a prognostic indicator in breast cancer.
The researchers found that, in vitro, DC-SCRIPT suppressed ER- and PR-mediated transcription in a ligand-dependent fashion, whereas it enhanced the activity of RARαand PPARγ.
In breast tissue samples from nine patients with breast cancer, DC-SCRIPT mRNA was expressed at significantly lower levels in the tumor than in the corresponding normal tissue.
Adema and team assessed the prognostic value of tumor DC-SCRIPT messenger (m)RNA expression in three independent cohorts of breast cancer patients.
They report that patients with high tumor DC-SCRIPT mRNA levels (DC-SCRIPT/porphobilinogen deaminase transcript ratio above 0.15) had a significantly longer disease-free interval than those with a low DC-SCRIPT mRNA level.
Further investigation revealed that the prognostic value was confined to patients with ER- and/or PR-positive tumors, where high tumor DC-SCRIPT mRNA levels were associated with a 54% to 84% reduced risk for recurrence, depending on the cohort.
In a combined analysis of all patients adjusted for tumor size, lymph node status, and adjuvant therapy, DC-SCRIPT level was an independent prognostic factor for breast cancer recurrence.
"On the basis of these findings, we hypothesize that the antiproliferative effect of DC-SCRIPT in breast cancer cells is mediated by modulating the activity of multiple nuclear receptors," write Adema and co-authors in the Journal of the National Cancer Institute.
They conclude: "It will be interesting therefore to also examine DC-SCRIPT expression levels in clinical trials that have explored the effect of stimulation of the RAR/retinoid X receptor (RXR) and PPARγ/RXR pathways on the clinical outcome in breast cancer patients."
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By Laura Dean