Hormone-dependent nuclear localization of the tyrosine kinase iyk in the normal human breast epithelium and loss of expression during carcinogenesis

iyk, a member of the frk family of non-receptor tyrosine kinases, was origi nally isolated from normal mouse mam mary glands and is characterized by a nuclear localizing signal within the SH2 domain. We have investigated the e xpression and subcellular localization of iyk in the normal human breast an d in malignant breast diseases. Immuno-histochemical analyses revealed that in normal tissue iyk localizes to both cytoplasmic and nuclear compartment s of breast epithelial cells, The subcellular distribution was dependent on the hormonal state, being mostly cytoplasmic during the follicular, prolif erative phase of the menstrual cycle, whereas frequent nuclear staining was observed in the resting stages during the luteal phase and, most prominent ly, after menopause. Strikingly, invasive carcinomas, irrespective of tumor type or hormonal status of the patient, exhibited almost complete loss of iyk expression in both the cytoplasm and the nucleus. In contrast, in situ breast carcinomas from post menopausal patients showed a clear reduction of the nuclear iyk localization while retaining cytoplasmic staining. Our res ults indicate that iyk expression is gradually lost during carcinogenesis; thus, iyk may be classified as a tumor-sup (C) 2000 Wiley-Liss, Inc.