The prognostic significance of BMP-6 signaling in prostate cancer

Yuen, Hiu‐Fung; Chan, Yuen-Piu; Cheung, Wai-Lok; Wong, Yi‐Lee; Wang, Xianghong; Chan, Kwok–Wah

doi:10.1038/modpathol.2008.94

Cited by 38 publications

(29 citation statements)

References 28 publications

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“…This correlated with a report that the BMP4 protein expression rate in NCC-RCC was higher than that in the clear-cell type [14]. BMP6 has been expressed higher in carcinomatous tissue of prostate or lung than in normal tissue; however, in the case of breast cancer the expression was higher in the normal tissue [8,12,29]. BMP6, in a dose-dependent manner, has an inhibitory effect on proliferation of kidney cancer cells which normally own BMPRII [15].…”

Section: Discussionsupporting

confidence: 75%

mRNA Expression of Bone Morphogenetic Proteins and Their Receptors in Human Renal Cell Carcinoma

Markić

Ćelić²,

Gršković

et al. 2011

Urol Int

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Introduction: Bone morphogenetic proteins (BMPs) have been studied in several cancers, but only limited information is available about renal cell carcinomas (RCCs). We determined the expression of mRNA of several BMP ligands and BMP receptors (BMPRs) in healthy kidney tissue and RCCs, and data were compared to clinicopathological parameters. Material and Methods: Sixty-four samples of RCCs and healthy renal tissues were prospectively examined. The expression of BMP2, BMP4, BMP6, BMP7, BMPRIA, BMPRIB and BMPRII mRNA was determined using semiquantitative reverse transcriptase-polymerase chain reaction. Results: The expression levels of different BMP ligands and BMPRs were considerably higher in RCCs than in normal kidney tissue. BMP ligands showed elevated expression in clear-cell RCCs, whereas all three BMPRs showed higher expression levels in non-clear-cell RCCs. In clear-cell RCCs, the expression levels of BMP2 progressively increased and expression levels of BMP6, BMP7 and BMPRIB were lost with higher tumor stage. Conclusions: All BMPs and their receptors have stronger expression levels in RCC. The expression level of BMP2 is strongly elevated in kidney cancer.

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Section: Discussionsupporting

confidence: 75%

mRNA Expression of Bone Morphogenetic Proteins and Their Receptors in Human Renal Cell Carcinoma

Markić

Ćelić²,

Gršković

et al. 2011

Urol Int

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“…Repression of several other genes, such as BMP-2, BMP-6, IL-8, and TGF-β, by SKI-606 is most likely beneficial. These genes have been shown to specifically promote the development of skeletal metastasis, an effect that can be reversed following down regulation of these genes (38)(39)(40)(41)(42). Overall results from these studies will lead to the identification of a panel of genes, change in the levels of expression of which can also be used as a marker for response to therapy with SFKs inhibitors in different cancers.…”

Section: Discussionmentioning

confidence: 99%

SKI-606 (Bosutinib) Blocks Prostate Cancer Invasion, Growth, and Metastasis In vitro and In vivo through Regulation of Genes Involved in Cancer Growth and Skeletal Metastasis

Rabbani

Valentino²,

Arakelian³

et al. 2010

Molecular Cancer Therapeutics

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In the current study, we have examined the efficacy of a Src/Abl kinase inhibitor SKI-606 (Bosutinib) for its effect on prostate cancer growth and skeletal metastasis. Treatment of highly invasive human prostate cancer cells PC-3 and DU-145 with different doses of SKI-606 decreased Src activation, cell proliferation, migration, and invasion as determined by Matrigel Boyden chamber invasion assay. For in vivo studies, PC-3 cells were inoculated through s.c. or i.t. route into male BALB/c nu/nu or Fox Chase severe combined immunodeficient mice, respectively. Experimental animals treated with SKI-606 developed tumors of a significantly smaller volume and a significant decrease (50%) in experimental skeletal lesion area. A marked increase (32%) in bone volume to tumor volume ratio was also seen by micro-computed tomography analysis of tibias from control and experimental groups of animals. Western blot analysis showed the ability of SKI-606 to significantly decrease the phosphorylation of signaling molecules (AKT, mitogen-activated protein kinase, focal adhesion kinase) and the expression of tumor progression-associated genes uPAR, MMP-2, MMP-9, N-cadherin, fibronectin, BMP-2 (bone morphogenetic protein 2), BMP-6 (bone morphogenetic protein 6), IL-8 (interleukin 8), and TGF-β (transforming growth factor β) in prostate cancer cells. SKI-606 is currently in clinical trials for breast cancer and chronic myelogenous leukemia. Results from these studies provide convincing evidence for evaluating its efficacy in prostate cancer patients. Mol Cancer Ther; 9(5); 1147-57.

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“…The expression patterns of different BMPs have been studied in multiple tumor types either at mRNA or at protein level. To mention a few, BMP6 is overexpressed in prostate cancer [14], BMP7 in colorectal cancer [15], and BMP2 in pancreatic cancer [16]. In contrast, BMP2 is downregulated in breast cancer [17].…”

Section: Introductionmentioning

confidence: 91%

Parallel inhibition of cell growth and induction of cell migration and invasion in breast cancer cells by bone morphogenetic protein 4

Ketolainen

Alarmo

Tuominen³

et al. 2010

Breast Cancer Res Treat

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Bone morphogenetic proteins (BMP) are extracellular signaling molecules that belong to the transforming growth factor β (TGFβ) superfamily. Bone morphogenetic proteins have diverse roles during development where they regulate proliferation, differentiation, and apoptosis in many different cell types by modulating the transcription of specific target genes. BMPs have also been implicated in both promotion and inhibition of cancer progression. We have recently shown that BMP4 is commonly expressed in breast cancer but its functional significance has not been previously explored. Our data demonstrate that in all nine breast cancer cell lines studied, BMP4 treatment leads to a dramatic growth suppression as a result of the induction of G1 arrest of the cell cycle. At the same time, BMP4 stimulates cell migration and invasion in a subset of these breast cancer cell lines. The BMP4-induced phenotypic changes were mediated through the activation of the canonical SMAD signaling pathway whereas no activation of MAP-kinases ERK1/2 or p38 was detected. Our results thus implicate that BMP4 is an important regulator of key phenotypic characteristics of cancer cells, cell growth, cell migration, and invasion, and that, similar to TGFβ, it possesses both tumor suppressive and oncogenic properties in breast cancer.

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The prognostic significance of BMP-6 signaling in prostate cancer

Cited by 38 publications

References 28 publications

mRNA Expression of Bone Morphogenetic Proteins and Their Receptors in Human Renal Cell Carcinoma

mRNA Expression of Bone Morphogenetic Proteins and Their Receptors in Human Renal Cell Carcinoma

SKI-606 (Bosutinib) Blocks Prostate Cancer Invasion, Growth, and Metastasis In vitro and In vivo through Regulation of Genes Involved in Cancer Growth and Skeletal Metastasis

Parallel inhibition of cell growth and induction of cell migration and invasion in breast cancer cells by bone morphogenetic protein 4

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