Bone morphogenetic protein 2 (BMP-2) induces sequential changes of Id gene expression in the breast cancer cell line MCF-7.
Bone morphogenetic proteins (BMPs) are involved in the development of various organs including the mammary gland. They are well-regulated and act in a time-, concentration- and cell-type-specific manner. We found that BMP-2 is expressed in primary breast tumor tissue samples and in breast cancer cell lines. Hybridization of labeled cDNA, obtained from the breast cancer cell line MCF-7, against the Atlas human cDNA expression array revealed differential gene expression depending on BMP-2 treatment. The most prominent changes were observed for the helix-loop-helix proteins Id-1, Id-2 and Id-3. Id-1 expression had increased severalfold after 4 h and was even higher after 24 h. Id-2 and Id-3 were more strongly induced after 4 h and showed no further significant change after 24 h. Analysis of cell-cycle distribution revealed a marked increase of the sub-G1 phase after 48 h in serum-deprived cells. In the presence of BMP-2 no change was observed over 48 h indicating that BMP-2 does not induce apoptosis. In addition, expression of caspase-3 was reduced in BMP-2-treated cells after 24 h. In summary, our results clearly indicate that BMP-2 is a susceptibility factor keeping the cells ready for the integration of various other signals for cell progression.
Clement
J H
JH
Department of Internal Medicine II, Friedrich Schiller University Jena, Germany. clement@polkim.med.uni-jena.de
Marr
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N
Meissner
A
A
Schwalbe
M
M
Sebald
W
W
Kliche
K O
KO
Höffken
K
K
Wölfl
S
S
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000502:physiology; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018257:Helix-Loop-Helix Motifs / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051798:Inhibitor of Differentiation Protein 1; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases