ORIGINAL PAPER Expression pattern of ATM and cyclin D1 in ductal carcinoma, normal adjacent and normal breast tissues of Iranian breast cancer patients Mahdieh Salimi • Hossein Mozdarani • Keivan Majidzadeh Received: 30 July 2011 / Accepted: 5 August 2011 / Published online: 18 August 2011 Ó Springer Science+Business Media, LLC 2011 Abstract ATM protein kinase plays a critical role in maintaining genome integrity by activating a biochemical chain reaction that in turn leads to cell cycle checkpoint activation and repair of DNA damage. Cyclin D1 acts in regulating the G1 phase of the cell cycle. Experimental and clinical studies suggest them to be involved in transfor- mation and tumour progression. To elucidate the role of ATM and cyclin D1 expression in sporadic breast cancer, we investigated the possible link between their RNA expression levels in ductal carcinoma and normal adjacent versus normal breast tissues measured by Taqman real- time PCR in 119 breast tissues. Results showed that cyclin D1 over-expressed in 51.4% of breast tumours, whereas ATM expression was down regulated in 55% of breast tumours compared to both normal adjacent and normal controls (P B 0.01). Cyclin D1 expression in adjacent normal and normal tissues was not significantly differed, whereas ATM expression in normal adjacent was lower than normal control (P B 0.01). Over-expression of cyclin D1 correlated with ER ? and/or PR ? (oestrogen/progester- one receptor) status, whereas it mostly under-expressed in HER2 ? (human epidermal growth factor 2) tumours. ATM under-expression was more observed in triple-negative tumours (ER - , PR - and HER2 - ). Our results indicated that reduced expression of the ATM and aberrant cyclin D1 expressions may contribute to the development and/or malignant progression of breast carcinomas also the latter could be involved in the regulation of hormone sensitivity associated with ER and PR. Keywords Sporadic breast cancer Á ATM Á Cyclin D1 Á RNA expression levels Á Ductal carcinoma Introduction Breast cancer is the most common malignancy includes a heterogeneous group of tumours with variable prognosis and a leading cause of death in women [1]. Its incidence is increasing worldwide. The estimated annual incidence of breast cancer worldwide is over one million cases, and there is a significant regional difference in the incidence rate: the high-risk areas North America and Northern Europe account for 16% of the worldwide population but 60% of the worldwide incidence of breast cancer [2]. In Iran, the incidence of the disease is rising, patients present with advanced stage of disease, and they are relatively younger (about 10 years) than their western counterparts [3–5]. Though at one of the lowest incidence rates in Iran as in other Asian countries, during last four decades, increasing its incidence rates has made breast cancer one of the most frequent malignancies among Iranian woman [6]. The mortality rate of breast cancer was 5.8 per 100,000 woman in Tehran in 1998 [4], 2.5 per 100,000 for female population and 7762 years life lost in the 18 provinces of Iran in 2001 [7]. A key event in tumourigenesis is the alteration of the genetic material, which modifies the expression of proteins in cell cycle progression [8] and/or repair of DNA altera- tions. The cell cycle is promoted by the activation of cyclin-dependent kinases, which are positively regulated M. Salimi Á H. Mozdarani (&) Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-111, Tehran, Iran e-mail: mozdarah@modares.ac.ir K. Majidzadeh Department of Cancer Genetics, Breast Diseases Research Centre, Enghelab Sq., Aboreihan St. Nazari St., Tehran, Iran 123 Med Oncol (2012) 29:1502–1509 DOI 10.1007/s12032-011-0043-5