Next Article in Journal
Sperm-Egg Fusion: A Molecular Enigma of Mammalian Reproduction
Next Article in Special Issue
The Diagnosis and Treatment of Pseudoprogression, Radiation Necrosis and Brain Tumor Recurrence
Previous Article in Journal
On the Influence of Crosslinker on Template Complexation in Molecularly Imprinted Polymers: A Computational Study of Prepolymerization Mixture Events with Correlations to Template-Polymer Recognition Behavior and NMR Spectroscopic Studies
Previous Article in Special Issue
MicroRNAs in Brain Metastases: Potential Role as Diagnostics and Therapeutics
Int. J. Mol. Sci. 2014, 15(6), 10635-10651; doi:10.3390/ijms150610635
Article

Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

1,2
, 3,4
, 5
, 6
, 1,7
 and 1,2,*
1 Laboratory of Neuro-Oncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 12, 10000 Zagreb, Croatia 2 Department of Biology, School of Medicine, University of Zagreb, Salata 3, 10000 Zagreb, Croatia 3 Ljudevit Jurak Department of Pathology, University Hospital "Sisters of Charity", 10000 Zagreb, Croatia 4 Department of Pathology, School of Medicine, University of Zagreb, Salata 10, 10000 Zagreb, Croatia 5 Department of Neurosurgery, University Hospital "Sisters of Charity", 10000 Zagreb, Croatia 6 Department of Radiology, University Hospital "Sisters of Charity", 10000 Zagreb, Croatia 7 Department of Internal Medicine, "Merkur" University Hospital, 10000 Zagreb, Croatia
* Author to whom correspondence should be addressed.
Received: 23 January 2014 / Revised: 14 May 2014 / Accepted: 27 May 2014 / Published: 13 June 2014
(This article belongs to the Special Issue Brain Metastasis 2014)
View Full-Text   |   Download PDF [1020 KB, uploaded 19 June 2014]   |   Browse Figures

Abstract

The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p = 0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.
Keywords: Dishevelled-1 (DVL1); Dishevelled-3 (DVL3); E-cadherin (CDH1); beta-catenin (CTNNB1); brain metastases; lung cancer; immunostaining; loss of heterozygosity Dishevelled-1 (DVL1); Dishevelled-3 (DVL3); E-cadherin (CDH1); beta-catenin (CTNNB1); brain metastases; lung cancer; immunostaining; loss of heterozygosity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


MDPI and ACS Style

Kafka, A.; Tomas, D.; Beroš, V.; Pećina, H.I.; Zeljko, M.; Pećina-Šlaus, N. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin. Int. J. Mol. Sci. 2014, 15, 10635-10651.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert