Differential expression and regulation of bone morphogenetic protein 7 in breast cancer.
Bone morphogenetic protein 7 (BMP-7) is an important regulator of cell development and differentiation of various organs. Tumorigenesis and tumor progression are also strongly associated with changes of the fate of cells which are highly differentiated in healthy tissues. Therefore, we studied the role of BMP-7 in breast cancer cell lines and in breast tumor tissue samples. BMP-7 is expressed in various cell lines, but in a cell line specific manner. The breast cancer cell lines MCF-7 and SK-BR-3 showed BMP-7 expression on the mRNA level. In T-47D we were not able to detect BMP-7 on the mRNA but on the protein level. Additionally, epidermal growth factor (EGF), a stimulator of proliferation, was not able to enhance BMP-7 expression on the transcriptional level. These findings are in contrast to the EGF-dependent regulation of BMP-6, indicating a differential regulation of these closely related TGF-beta members. In order to confirm the data obtained from cell cultures, we analyzed normal breast tissue and tumor tissue samples from 170 invasive ductal carcinomas of the breast by immunohistochemistry. We found BMP-7 expression in normal breast tissue in the end buds, but not in the ductus lactiferus. BMP-7 protein was detected in all 170 tumor samples. Comparing BMP-7 levels with histopathological parameters, we could not show a correlation of BMP-7 and the proliferation index nor with erbB receptors. But the expression of BMP-7 was highly correlated with estrogen receptor levels (p< or=0.01) and progesterone receptor levels (p< or =0.01) which are important markers for breast cancer prognosis and therapy.
Schwalbe
Manuela
M
Department of Internal Medicine II, Friedrich Schiller University Jena, Forschungszentrum Lobeda, Erlanger Allee 101, D-07740 Jena, Germany.
Sänger
Jörg
J
Eggers
Ralf
R
Naumann
Anke
A
Schmidt
Andreas
A
Höffken
Klaus
K
Clement
Joachim H
JH
D015153:Blotting, Western; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D011379:Prognosis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta
C525816:BMP6 protein, human; C525819:BMP7 protein, human; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D012313:RNA