title: A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7.
abstract: Bone morphogenetic proteins (BMPs) regulate diverse cellular processes, such as proliferation, differentiation, and apoptosis. The BMPs have been studied in several cancers, but thus far contradictory results have been obtained and, especially in breast cancer, information on BMPs is still limited. We performed a systematic expression survey of BMPs and their receptors in breast cancer. mRNA expression was studied of seven BMP ligands (BMP2-BMP8) and six receptors (ACVR1, BMPR1A, BMPR1B, BMPR2, ACVR2A, and ACVR2B) that specifically mediate BMP signals. Expression levels were determined in 22 breast cancer cell lines, 39 primary breast tumors, normal human mammary epithelial cell line, and normal mammary gland using semiquantitative RT-PCR. The expression frequencies and expression levels of different BMPs varied considerably in breast cancer with BMP4 and BMP7 being most frequently expressed and showing highest expression levels. The BMP specific receptors were more uniformly expressed and indicated that breast cancer is fully capable of transmitting BMP signals. Expression frequencies and levels for both the ligands and the receptors were in good concordance between the breast cancer cell lines and primary tumors. We can conclude that breast cancers possess functional BMP signaling machinery on the cell surface with distinct differences in the expression of various BMP ligands. Our survey focuses the attention particularly toward BMP4 and BMP7 and suggests their importance in breast cancer. Breast cancer cell lines and the data generated here serve as a good resource for further studies on BMP function in breast cancer.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Biokatu 6, Tampere, Finland.
authors.forename: Emma-Leena
authors.initials: EL
authors.lastname: Alarmo
authors.forename: Tuula
authors.initials: T
authors.lastname: Kuukasjärvi
authors.forename: Ritva
authors.initials: R
authors.lastname: Karhu
authors.forename: Anne
authors.initials: A
authors.lastname: Kallioniemi
mesh_terms: D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000032:analysis; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000032:analysis; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: C525809:BMP4 protein, human; C525819:BMP7 protein, human; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II