SPORADIC AMPLIFICATION OF THE INSULIN-RECEPTOR GENE IN HUMAN BREAST-CANCER

Insulin receptor (IR) content is increased in most human breast carcin omas when compared to normal breast tissue, In the present study we in vestigated IR gene copy number by using both conventional DNA analysis (slot blot) and fluorescence in situ hybridization (FISH). Cultured h uman breast cell lines and primary breast carcinoma specimens were ana lyzed, In 6 breast cell lines in culture both techniques gave similar results: the relative IR copy number determined by FISH strongly corre lated with slot blot results (r = 0.831), even if probes for different reference loci were used in the 2 methods. We find that in human brea st cancer IR gene amplification isa sporadic event. It occurred in 1/5 cultured breast cancer cell lines (MDA-MB 231) and in 8/93 (8.6%) bre ast cancer specimens. In contrast an increased copy number of the enti re chromosome 19 (which contains IR gene) was frequently observed in b oth breast cancer cell lines (100%) and breast cancer specimens (45%). When present, IR gene amplification always occurred at low level. The se data indicate that IR gene amplification is an uncommon event in hu man breast carcinomas and that mechanisms other than gene amplificatio n are responsible for IR protein overexpression in most human breast c ancers. (C)1997, Editrice Kurtis.