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Expression of bone morphogenetic protein 6 in normal mammary tissue and breast cancer cell lines and its regulation by epidermal growth factor
Author(s) -
Clement Joachim H.,
Sänger Jörg,
Höffken Klaus
Publication year - 1999
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(19990118)80:2<250::aid-ijc14>3.0.co;2-d
Subject(s) - amphiregulin , epidermal growth factor , endocrinology , biology , medicine , bone morphogenetic protein , growth factor , cancer research , epidermal growth factor receptor , cancer , receptor , biochemistry , gene
Bone morphogenetic proteins (BMPs) are multifunctional regulators of proliferation, differentiation and apoptosis. BMP‐6 is involved in numerous developmental processes. We have demonstrated expression of BMP‐6 in breast cancer cell lines by RT‐PCR and immuno‐histochemistry. The level of BMP‐6 mRNA decreased upon serum starvation, whereas epidermal growth factor (EGF) treatment led to elevation of BMP‐6 mRNA levels in a dose‐dependent manner, with a maximum at 50 ng/ml EGF under serum‐free conditions in hormone‐sensitive (MCF‐7) and in hormone‐insensitive (SK‐BR‐3) breast cancer cell lines. The EGF‐like growth factors transforming growth factor‐α, amphiregulin and betacellulin were also able to elevate the BMP‐6 mRNA level after 24 hr. Inhibition of EGF receptor tyrosine kinase with tyrphostine AG1517 repressed the inductive effect of these growth factors, indicating an EGF receptor‐mediated regulation of BMP‐6 mRNA. In addition, BMP‐6 mRNA was detected in tumor samples from breast carcinoma patients. However, levels were reduced in 18/44 samples compared with tumor‐free resection margins. In 12 of these 18 patients, at least a 10‐fold reduction of EGF receptor mRNA levels in tumor samples vs. tumor‐free samples was observed. This suggests a putative relationship between EGF receptor and BMP‐6 mRNA levels in breast cancer. Int. J. Cancer 80:250–256, 1999. © 1999 Wiley‐Liss, Inc.