What do we know about ATM protein expression in breast tissue?

The great majority of breast cancer cases are not associated with a mutated gene of high penetrance such as BRCA1 BRCA2 and TP53. Genes of low penetra nce, frequently mutated in the general population, might play an important role in breast cancer development. The ATM gene, which encodes the ATM prot ein, mutated in the disorder ataxia telangiectasia (AT) could be such a sus ceptibility gene. Indeed, 1% of the general population is estimated to be A T heterozygote and females have an increased risk of developing breast canc er. The A TM protein is involved in the signalling pathway of DNA double-st rand breaks. Studies on its expression in normal breast tissues have shown that A TM is expressed in the epithelial cells of breast ducts, but not in the myoepithelial cells. In sclerosing adenosis, a benign lesion of the bre ast, the ATM protein is expressed in both cell types whereas its expression is absent or reduced in tumour epithelial cells in about 30-50% of invasiv e carcinomas. Moreover, the study of the p53 status in some of these tumour s has revealed that the ATM/p53 signalling pathway is frequently altered ei ther by a very low ATM expression or by the presence of a mutated p53 It re mains to be determined whether alterations in the expression of other prote ins also involved in this DNA damage signalling cascade are specifically as sociated with breast cancer development and/or a radiosensitive phenotype s een in some breast cancer patients after radiotherapy.