Expression of bone morphogenetic protein 2 in breast cancer cells inhibits hypoxic cell death

Raida, Martin; Clement, Joachim H.; Ameri, Kurosh; Chen, Han; Leek, Russell; Harris, Adrian L.

doi:10.3892/ijo.26.6.1465

Cited by 38 publications

(45 citation statements)

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“…Many studies report on alterations of the BMP pathway in several tumor systems, including breast, prostate, lung, and colon cancers, as well as glioblastoma, osteosarcoma and MB (Arihiro and Inai, 2001;Langenfeld et al, 2003;Miyazaki et al, 2004;Raida et al, 2005;Piccirillo and Vescovi, 2006;Ye et al, 2007;Buijs et al, 2007a;Dai et al, 2008). Similar to other transforming growth factor-b members (Derynck et al, 2001), BMPs may have a dual role in cancer, both promoting and repressing tumorigenesis in several models (Buijs et al, 2007a, b;Ye et al, 2009;Thawani et al, 2010).…”

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confidence: 99%

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

et al. 2011

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Medulloblastoma (MB) is the most common malignant brain tumor in children. It is known that overexpression and/or amplification of the MYC oncogene is associated with poor clinical outcome, but the molecular mechanisms and the MYC downstream effectors in MB remain still elusive. Besides contributing to elucidate how progression of MB takes place, most importantly, the identification of novel MYC-target genes will suggest novel candidates for targeted therapy in MB. A group of 209 MYC-responsive genes was obtained from a complementary DNA microarray analysis of a MB-derived cell line, following MYC overexpression and silencing. Among the MYC-responsive genes, we identified the members of the bone morphogenetic protein (BMP) signaling pathway, which have a crucial role during the development of the cerebellum. In particular, the gene BMP7 was identified as a direct target of MYC. A positive correlation between MYC and BMP7 expression was documented by analyzing two distinct sets of primary MB samples. Functional studies in vitro using a small-molecule inhibitor of the BMP/SMAD signaling pathway reproduced the effect of the small interfering RNA-mediated silencing of BMP7. Both approaches led to a block of proliferation in a panel of MB cells and to inhibition of SMAD phosphorylation. Altogether, our findings indicate that high MYC levels drive BMP7 overexpression, promoting cell survival in MB cells. This observation suggests the potential relevance of targeting the BMP/SMAD pathway as a novel therapeutic approach for the treatment of childhood MB.

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Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

et al. 2011

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“…Therapeutic targets for breast cancers include not only the binding of estrogen to ER but also the activity of estrogenic enzymes in the tumor tissues [105]. There have been several reports showing the expression of some of TGF-β superfamily proteins, such as BMP-2 [106], -6 [107], and -7 [108] in breast cancer cells, in which their possible role in breast cancer development and involvement in bone metastasis has been discussed [109,110]. Furthermore, the involvement of BMPSmad activation in the progression and dedifferentiation of ER-positive breast cancer was recently reported [111].…”

Section: Bmp System In the Thyroid Suppresses Tsh Receptor Signalingmentioning

confidence: 99%

Multiple Endocrine Regulation by Bone Morphogenetic Protein System

Otsuka

2010

Endocr J

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Abstract. Bone morphogenetic proteins (BMPs) were originally identified with regard to their actions to regulate ectopic formation of bone and cartilage and early embryonic development. Subsequently, our research program has investigated a BMP system that exists in the mammalian ovary and plays roles in regulating numerous granulosa cell functions. BMP ligands including BMP-2, -4, -6, -7 and -15 were found to inhibit gondotropin-dependent progesterone synthesis by granulosa cells, which led to the hypothesis that BMPs are a physiological luteinization inhibitor in growing ovarian follicles during the follicular phase of the ovarian cycle. The physiological importance of the BMP system for normal mammalian reproduction has been further recognized by the discovery of aberrant reproductive phenotypes of female sheep and humans having mutated genes encoding BMP-15. Physiological roles of BMPs in the pituitary, hypothalamus, adrenal and other tissues have also been discovered. Here we discuss recent advances in the understanding of autocrine/paracrine actions of BMPs in the systemic regulation of endocrine function.Key words: Bone morphogenetic protein, Folliculogenesis, Ovary, Reproduction, Steroidogenesis Bone morphogenetic proteins (BmPs) were originally isolated from bone tissues as proteins that induce bone and cartilage formation in ectopic extra-skeletal sites in vivo [1]. The amino acid sequences from the corresponding cDNAs revealed that BmP ligands are structurally classified into transforming growth factor (TGF)-β superfamily member. To date, more than 30 members of the TGF-β superfamily have been identified in various species [2,3]. There is no direct evidence that all molecules designated as BMPs can induce cartilage and/or bone formation, whereas it has been well established that BMPs regulate multiple biological processes including cell proliferation, apoptosis, differentiation and morphogenesis. in this review, the recent advances regarding critical BmP actions in the ovarian folliculogenesis, which has been mostly discovered by Shimasaki's laboratory [4,5], and in many of extra-gonadal endocrine tissues are introduced. i) molecular characteristics and receptor signaling of the Bmp systemLigands of the TGF-β superfamily are initially synthesized as large precursor proteins. The precursor proteins dimerize and then are cleaved by proteolytic processing to produce mature dimeric proteins. The BMPs are distinguished from other members by having seven, rather than nine, conserved cysteine residues in the mature region. Six of the seven common cysteines in the mature protein are linked within the subunit to form a rigid structure called a "cysteine knot." The re-

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“…In an in vivo breast cancer to bone metastasis model, the presence of BMP-2 in a scaffold increased the metastatic frequency of the breast cancer cell line SUM1315 (Moreau et al, 2007). On the other hand, treatment with BMP-2 in the breast cancer cell line C2C12 resulted in increased expression of Id-1 (Katagiri et al, 1994;Nobta et al, 2005;Raida et al, 2005;Langenfeld et al, 2006), while BMP-2 also positively regulated the expression of Id-1 in certain cell contexts (Locklin et al, 2001;Takeda et al, 2004). Because BMPs have very important roles in the development of bone metastasis in prostate cancer cells (Feeley et al, 2005(Feeley et al, , 2006, it might be possible that BMP-2 in the bone environment promotes metastasis of cancer cells to bone through upregulation of the intrinsic expression of Id-1 in cancer cells.…”

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Prostate cancer cells modulate osteoblast mineralisation and osteoclast differentiation through Id-1

Chan

et al. 2009

Br J Cancer

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BACKGROUND: Id-1 is overexpressed in and correlated with metastatic potential of prostate cancer. The role of Id-1 in this metastatic process was further analysed. METHODS: Conditioned media from prostate cancer cells, expressing various levels of Id-1, were used to stimulate pre-osteoclast differentiation and osteoblast mineralisation. Downstream effectors of Id-1 were identified. Expressions of Id-1 and its downstream effectors in prostate cancers were studied using immunohistochemistry in a prostate cancer patient cohort (N ¼ 110). RESULTS: We found that conditioned media from LNCaP prostate cancer cells overexpressing Id-1 had a higher ability to drive osteoclast differentiation and a lower ability to stimulate osteoblast mineralisation than control, whereas conditioned media from PC3 prostate cancer cells with Id-1 knockdown were less able to stimulate osteoclast differentiation. Id-1 was found to negatively regulate TNF-b and this correlation was confirmed in human prostate cancer specimens (P ¼ 0.03). Furthermore, addition of recombinant TNF-b to LNCaP Id-1 cell-derived media blocked the effect of Id-1 overexpression on osteoblast mineralisation. CONCLUSION: In prostate cancer cells, the ability of Id-1 to modulate bone cell differentiation favouring metastatic bone disease is partially mediated by TNF-b, and Id-1 could be a potential therapeutic target for prostate cancer to bone metastasis.

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Expression of bone morphogenetic protein 2 in breast cancer cells inhibits hypoxic cell death

Cited by 38 publications

References 0 publications

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma

Multiple Endocrine Regulation by Bone Morphogenetic Protein System

Prostate cancer cells modulate osteoblast mineralisation and osteoclast differentiation through Id-1

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