Enhancement of mdr1 gene expression in normal tissue adjacent to advanced breast cancer

In the present study, mdr1 gene expression was investigated by a sensitive reverse transcriptase-PCR assay in advanced breast cancer and in correspond ing adjacent normal tissues obtained before and after treatment with primar y chemotherapy. Comparatively to normal tissues, a significant induction of mdr1 expression was observed in untreated tumors (p=0.0222). Similarly, a significant induction of mdr1 expression was revealed when treated samples were compared to untreated counterparts (p=0.0222), but no differences were detected between tumor and normal samples (p=0.3199). Noteworthy, a signif icant induction of mdr1 gene expression occurred in treated normal samples comparatively to untreated ones (p=0.0037), and this induction was even mor e important in normal than in tumoral tissue (p=0.0627). However, neither t he basal expression nor the induction of mdr1 were correlated with subseque nt response to chemotherapy or with survival. Thus, in agreement with previ ous reports, our data show that chemotherapy induce mdr1 gene expression in breast cancer cells, but they also indicate that a similar phenomenon occu rs in adjacent normal tissues. Therefore, our results strongly suggest that mdr1 gene overexpression is not a characteristic of breast malignant cells , but rather constitutes a general phenomenon occurring both in normal and tumor cells which could explain at least in part the absence of relationshi p between mdr1 expression and the clinical outcome of breast cancer patient s.