Sequence analysis of the DNA binding domain of the estrogen receptor gene in ER (+)/PR (-) breast cancer.
Estrogen stimulates the proliferation of breast cancer cells and regulates the expression of other proteins, including the progesterone receptor (PR), via interaction with a unique estrogen receptor (ER), a ligand-inducible transcription factor that binds to regulatory DNA sequences associated with target genes. The best indirect evidence of an intact ER gene signaling system in a tumor is the demonstration of both ER and PR cytosol protein. The molecular basis of the ER (+)/PR (-) phenotype is unknown and may reflect either defective PR gene expression or alterations in the ER-specifically, inability of the ligand-receptor complex to effectively bind to regulatory sequences in DNA. To test the latter possibility, we evaluated 10 ER (+)/PR (-) resected human breast cancers for small deletions and point mutations in the DNA binding domain of the ER gene. Exons 2 and 3 and their flanking intron sequences were selectively amplified using the polymerase chain reaction and then directly sequenced using the Sanger dideoxynucleotide method. A normal gene sequence was found in all cases studied. We conclude that sequence aberrations in the DNA binding domain of the ER are not a common cause of absent PR expression in ER (+)/PR (-) breast carcinomas.
Mies
C
C
Department of Pathology, University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Florida, USA.
Voigt
W
W
D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis*; D006801:Humans; D011485:Protein Binding / Q000235:genetics; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D017422:Sequence Analysis, DNA
D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone