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Hormone‐dependent nuclear localization of the tyrosine kinase iyk in the normal human breast epithelium and loss of expression during carcinogenesis
Author(s) -
Berclaz Gilles,
Altermatt Hans Jörg,
Rohrbach Valeria,
Dreher Ekkehard,
Ziemiecki Andrew,
Andres AnneCatherine
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000315)85:6<889::aid-ijc25>3.0.co;2-4
Subject(s) - biology , carcinogenesis , subcellular localization , cell nucleus , cytoplasm , mammary gland , follicular phase , pathology , breast cancer , nuclear localization sequence , epithelium , luteal phase , tumor suppressor gene , cancer , cancer research , endocrinology , microbiology and biotechnology , medicine , genetics
iyk, a member of the frk family of non‐receptor tyrosine kinases, was originally isolated from normal mouse mammary glands and is characterized by a nuclear localizing signal within the SH2 domain. We have investigated the expression and subcellular localization of iyk in the normal human breast and in malignant breast diseases. Immuno‐histochemical analyses revealed that in normal tissue iyk localizes to both cytoplasmic and nuclear compartments of breast epithelial cells. The subcellular distribution was dependent on the hormonal state, being mostly cytoplasmic during the follicular, proliferative phase of the menstrual cycle, whereas frequent nuclear staining was observed in the resting stages during the luteal phase and, most prominently, 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 results indicate that iyk expression is gradually lost during carcinogenesis; thus, iyk may be classified as a tumor‐suppressor gene. Int. J. Cancer 85:889–894, 2000. © 2000 Wiley‐Liss, Inc.