Genetic events during the transformation of a tamoxifen-sensitive human breast cancer cell line into a drug-resistant clone

• Published in: Cancer genetics and cytogenetics 2001-10, Vol.130 (2), p.166-172
• Main Authors: Achuthan, Rajgopal, Bell, Sandra M, Roberts, Paul, Leek, Jack P, Horgan, Kieran, Markham, Alexander F, MacLennan, Kenneth A, Speirs, Valerie
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Hormonal - pharmacology; Biological and medical sciences; Breast Neoplasms - genetics; Cell Transformation, Neoplastic - genetics; Chromosome Aberrations; Chromosome Painting; Cytogenetic Analysis; Drug Resistance, Neoplasm - genetics; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Nucleic Acid Hybridization; Tamoxifen - pharmacology; Tumor Cells, Cultured; Tumors
• ISSN: 0165-4608; 1873-4456
• DOI: 10.1016/S0165-4608(01)00475-7

Tamoxifen resistance is a serious clinical problem commonly encountered in the management of patients with breast cancer. The mechanisms leading to its development are unclear. Tamoxifen acts via multiple pathways and has diverse effects. Hence transformation from a tamoxifen-sensitive to a resistant phenotype could involve multiple genetic events. Knowledge of the genetic pathways leading to resistance may facilitate the development of novel therapeutic strategies. In this study, a variation of conventional comparative genomic hybridization (CGH) has been employed to detect genetic alterations associated with tamoxifen resistance. MCF-7, a tamoxifen-sensitive human breast cancer cells line, and its tamoxifen-resistant clone, CL-9 were used. Both cell lines showed extensive areas of concordance but consistent differences were seen with the acquisition of tamoxifen resistance. These differences included the amplification of 2p16.3∼p23.2, 2q21∼q34, 3p12.3∼p14.1, 3p22∼p26, 3q, 12q13.2∼q22, 13q12∼q14, 17q21.3∼q23, 20q11.2∼q13.1 and 21q11.2∼q21 as well as the deletion of 6p21.1, 6p23∼p25, 7q11.1∼q31, 7q35∼q36, 11p15, 11q24, 13q33, 17p, 18q12∼q21.1, 19p, 19q13.3, 22q13.1∼q13.2. These findings were supported by conventional cytogenetics and chromosome painting. The regions identified by CGH potentially harbor genes that could be important in the development of tamoxifen resistance.