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 corresponding adjacent normal tissues obtained before and after treatment with primary 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 significant induction of mdr1 gene expression occurred in treated normal samples comparatively to untreated ones (p = 0.0037), and this induction was even more important in normal than in tumoral tissue (p = 0.0627). However, neither the basal expression nor the induction of mdr1 were correlated with subsequent response to chemotherapy or with survival. Thus, in agreement with previous reports, our data show that chemotherapy induce mdr1 gene expression in breast cancer cells, but they also indicate that a similar phenomenon occurs 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 relationship between mdr1 expression and the clinical outcome of breast cancer patients.
Arnal
M
M
Laboratory of Molecular Genetic, Inserm U-517, Centre Georges François Leclerc, Dijon, France.
Franco
N
N
Fargeot
P
P
Riedinger
J M
JM
Brunet-Lecomte
P
P
Lizard-Nacol
S
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil