Estrogen receptor-alpha, bcl-2 and c-myc gene expression in fibroadenomas and adjacent normal breast: association with nodule size, hormonal and reproductive features.
Fibroadenomas are the most common benign lump in females. The study of gene alterations and/or deregulation in reproductive years may help explain hormonal physiological processes involved in nodule development and evolution. The objective was to compare ER-alpha, c-myc, and bcl-2 gene expression in breast fibroadenomas and in normal tissue and evaluate menstrual cycle, parity, and oral contraceptive influences. Fifty-seven premenopausal women (14-49 years) undergoing surgical removal of fibroadenomas were selected. Samples from fibroadenomas and circumjacent normal tissue were obtained for RT-PCR paired analysis. Patients were divided in groups according to menstrual cycle, use of contraceptives and parity. Tissue from 32 patients was adequate for RT-PCR. Paired analysis showed higher expression of ER-alpha (P=0.012) and bcl-2 (P=0.001) in fibroadenomas than in normal breast, while c-myc presented a similar expression (P=0.655). ER-alpha was higher in fibroadenomas of patients in follicular phase versus contraceptive users and normal tissue (P=0.003); bcl-2 was higher in fibroadenomas of patients in luteal phase than in the normal samples from all groups (P=0.007). c-myc did not differ according to menstrual cycle, but was higher in fibroadenomas>3 cm versus<3 cm (P=0.015) and in nulliparous women (P=0.04). A positive correlation between c-myc levels and fibroadenoma diameter was demonstrated (r=0.536; P=0.007). Nulliparous mean nodule diameter was superior than parous women (P=0.008). In conclusion, the expression of ER-alpha, bcl-2 and c-myc depends on hormonal and reproductive factors, with a possible contribution to lump formation and evolution.
Cericatto
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R
Laboratory of Molecular Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rua Sarmento Leite, 500, Porto Alegre 90050-170, RS, Brazil.
Pozzobon
A
A
Morsch
D M
DM
Menke
C H
CH
Brum
I S
IS
Spritzer
P M
PM
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000737:chemistry*; D005260:Female; D018226:Fibroadenoma / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D017697:Premenopause; D011374:Progesterone / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D011374:Progesterone; D012313:RNA