A gene dosage effect is responsible for high overexpression of the MUC1 gene observed in human breast tumors.
Alterations of the entire long arm of chromosome 1 are the most consistent cytogenetic abnormalities found in human breast carcinoma. Overexpression of a large number of genes, because of acquisition of additional copies of one arm or a whole chromosome, is one possible cause of the imbalance in cell metabolism. To investigate the existence of such a gene dosage effect in breast cancer, we chose to study the MUC1 mucin gene located at 1q21-q24. This gene is highly expressed in breast tumors, but the genetic mechanism for its ectopic overexpression is not clearly known. Thirty-two human primary breast tumors were examined, by Southern blot DNA and northern blot RNA analyses, for allelic dosage and expression of the MUC1 gene. A correlation was found between acquisition of additional copies of MUC1 gene and high mRNA levels (p < 0.0001). These results identify a genetic mechanism responsible for MUC1 gene overexpression and support the hypothesis that a gene dosage effect of the long arm of chromosome 1 may be involved in the pathogenesis of breast cancer.
Bièche
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Laboratoire d'Oncogénétique, Centre René Huguenin, St-Cloud, France.
Lidereau
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D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D018628:Gene Dosage; D006801:Humans; D018396:Mucin-1 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D004273:DNA, Neoplasm; D018396:Mucin-1; D012333:RNA, Messenger; D004247:DNA