Allelic imbalance at 11q23-q24 chromosome associated with estrogen and radiation-induced breast cancer progression

• Published in: International journal of oncology Vol. 28; no. 3; pp. 667 - 674
• Main Authors: ROY, D, CALAF, G. M, HANDE, M. P, HEI, T. K
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01-03-2006
• Subjects: Alpha Particles; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Line, Transformed; Cell Line, Tumor; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - radiation effects; Chromosomes, Human, Pair 11 - genetics; Estrogens - pharmacology; Female; Gynecology. Andrology. Obstetrics; Humans; In Situ Hybridization, Fluorescence - methods; Loss of Heterozygosity; Mammary gland diseases; Medical sciences; Microsatellite Repeats - genetics; Tumors; Mammary gland diseases; Cancerology; Allelic imbalance; Estrogen; Tumor progression; Genetics; Breast cancer; Malignant tumor; Sex steroid hormone; Chromosome C11; Ovarian hormone
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.28.3.667

Multiple genetic alterations are common in cancers including those of the breast. The mechanisms leading to these alterations such as point mutations, gene amplifications, deletions and replication error are often associated with frequent and consistent loss of heterozygosity (LOH) or microsatellite instability (MSI). Several cytological and molecular studies have shown high frequency loss of genetic information on the long arm of chromosome 11 (i.e., 11q) in various primary breast cancers. In the present study allelic alterations in a refined position on the long arm of chromosome 11 were studied to identify the spectrum of induced damage at different stages of malignant transformation of MCF-10F cell lines after exposure to high-LET radiation using alpha-particles and exposure to estradiol by using PCR-single strand conformation polymorphism (SSCP) and fluorescence in situ hybridization (FISH) analysis. Microsatellite markers were selected from chromosome 11 (11q23-q24 loci) and it was found that frequency of allelic imbalance occurs at different stages of tumor progression with a range of 15-45% depending on the marker studied. These results strongly suggested the presence of several tumor suppressor genes in this critical region of chromosome 11 (11q23-q24). It also represents the first indication of allele loss at these loci in human breast epithelial cells induced by radiation and estrogen treatment suggesting a potential interventional target in breast carcinogenesis.