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

Ketolainen, Johanna; Alarmo, Emma-Leena; Tuominen, Vilppu J.; Kallioniemi, Anne

doi:10.1007/s10549-010-0808-0

Cited by 68 publications

(97 citation statements)

References 54 publications

(81 reference statements)

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“…We have previously shown that BMP4 mRNA is expressed at variable levels in a small panel of primary breast tumors. 23,33 Similarly to our previous observations, the majority of patient samples also displayed a relatively low BMP4 protein expression level. In 23% of the samples, BMP4 was expressed in a strong granular manner.…”

Section: Discussionsupporting

confidence: 85%

“…In the normal mammary gland tissue, BMP4 was detected only at a low level implying that strong expression is cancer specific. In our previous study, BMP4 mRNA expression was observed more often in low-grade tumors, 23 but this observation did not translate to the protein level. However, strong BMP4 expression was more common in invasive lobular carcinomas than in ductal carcinomas.…”

Section: Discussionmentioning

confidence: 70%

“…A control with no BMP4 antibody showed no staining. To further verify the specificity of the BMP4 antibody, immunocytochemical staining of breast cancer cell lines with high (HCC38) and low/no (HCC1954) BMP4 mRNA expression 23 was performed and revealed strong and no expression, respectively.…”

Section: Bmp4 Immunohistochemistrymentioning

confidence: 99%

“…17 In these studies, BMP4 has been functionally linked to the reduced growth of prostate, breast and pancreatic cancer cells, the increased migration and invasion of breast, colorectal, ovarian, melanoma and pancreatic cancer cells, the induction of the epithelialmesenchymal transition in ovarian and pancreatic cancer cells and to lung cancer cell senescence. [18][19][20][21][22][23][24][25] Interestingly, BMP4 has also recently been identified as a new susceptibility locus for colorectal cancer. 26 BMP4 expression has been detected in various cancer cell lines and tumor cells, but often, the number of samples included in these studies has been low.…”

mentioning

confidence: 99%

“…32 We have previously shown that BMP4 is strongly expressed in breast cancer cell lines and primary breast tumors. 23,33 Furthermore, we proposed a bidirectional function for BMP4 as in vitro it reduced cancer cell proliferation and yet was able to simultaneously increase the migration and invasion of breast cancer cells. 23 Currently, no studies exploring BMP4 protein expression in breast tumors have been conducted.…”

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confidence: 99%

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Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Alarmo¹,

Huhtala

Korhonen

et al. 2013

Modern Pathology

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Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor b (TGFb) superfamily and are known to regulate cell proliferation, differentiation and motility, especially during development. BMP4 has an indispensable role in vertebrate development while limited information on BMP4 expression and function exists in adult tissues. Nevertheless, its contribution to cancer development and progression has gained increasing interest in recent years. Functional studies, especially in breast cancer, have implicated BMP4 both in inhibition of cell proliferation and in promotion of cell migration and invasion. To gain an insight into the function of BMP4 in normal and cancer tissues, BMP4 protein expression levels were analyzed by immunohistochemistry in 34 different normal organs/tissues, 34 different tumor types and finally in 486 breast cancer samples where possible associations between BMP4 and clinicopathological parameters were statistically evaluated. In over 20% of normal and malignant tissues, BMP4 was expressed at high level. Strong expression was observed particularly in some normal epithelial cells, such as bladder and stomach, and in squamous cell carcinomas. In breast cancer, strong BMP4 expression was detected in 25% of patients, and was associated with low proliferation index and increased frequency of tumor recurrence. Taken together, BMP4 is expressed in a subset of normal adult tissues and is likely to contribute to tissue homeostasis. However, in tumors, BMP4 expression levels vary considerably, implying diverse roles in different tumor types. This role is biphasic in breast cancer as BMP4 expression is linked to reduced proliferation and increased recurrence, thus corroborating our previous in-vitro functional data.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 70%

Section: Bmp4 Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Alarmo¹,

Huhtala

Korhonen

et al. 2013

Modern Pathology

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Electrosynthesis of Highly Transparent Cobalt Oxide Water Oxidation Catalyst Films from Cobalt Aminopolycarboxylate Complexes

et al. 2015

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Efficient catalysis of water oxidation represents one of the major challenges en route to efficient sunlight-driven water splitting. Cobalt oxides (CoOx ) have been widely investigated as water oxidation catalysts, although the incorporation of these materials into photoelectrochemical devices has been hindered by a lack of transparency. Herein, the electrosynthesis of transparent CoOx catalyst films is described by utilizing cobalt(II) aminopolycarboxylate complexes as precursors to the oxide. These complexes allow control over the deposition rate and morphology to enable the production of thin, catalytic CoOx films on a conductive substrate, which can be exploited in integrated photoelectrochemical devices. Notably, under a bias of 1.0 V (vs. Ag/AgCl), the film deposited from [Co(NTA)(OH2 )2 ](-) (NTA=nitrilotriacetate) decreased the transmission by only 10 % at λ=500 nm, but still generated >80 % of the water oxidation current produced by a [Co(OH2 )6 ](2+) -derived oxide film whose transmission was only 40 % at λ=500 nm.

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Both inhibition and enhanced expression of miR‐31 lead to reduced migration and invasion of pancreatic cancer cells

Laurila

Sandström

Rantanen

et al. 2012

Genes Chromosomes & Cancer

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MicroRNAs (miRNAs) are short single-stranded RNA molecules that have a critical role in the regulation of gene expression. Alterations in miRNA expression levels have been observed in multiple tumor types and there is clear evidence on their active involvement in cancer development. Here, a comprehensive miRNA expression profiling in 16 pancreatic cancer cell lines and four normal pancreatic samples provided a specific molecular signature for pancreatic cancer and enabled us to identify 72 differentially expressed miRNAs with approximately half of them being up- and half downregulated in cancer cells as compared with normal samples. Of these, miR-31 was selected for further functional analyses based on its interesting "on-off" type expression profile, i.e., very low or even absent expression in normal pancreas and in six of the pancreatic cancer samples but extremely high expression in the remaining 10 cell lines. Quite unexpectedly, both the inhibition of miR-31 in AsPC-1 and HPAF-II pancreatic cancer cells with high endogenous expression and forced expression of miR-31 in MIA PaCa-2 with low endogenous levels led to reduced cell proliferation, migration, and invasion. More importantly, in AsPC-1 cells further enhancement of miR-31 also resulted in reduced cell migration and invasion, implicating that the level of miR-31 is critical for these phenotypes. This study highlights a specific miRNA expression pattern in pancreatic cancer and reveals that manipulation of miR-31 expression leads to reduced cell migration and invasion in pancreatic cancer.

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

Cited by 68 publications

References 54 publications

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Electrosynthesis of Highly Transparent Cobalt Oxide Water Oxidation Catalyst Films from Cobalt Aminopolycarboxylate Complexes

Both inhibition and enhanced expression of miR‐31 lead to reduced migration and invasion of pancreatic cancer cells

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