Tumor suppressor gene E-cadherin and its role in normal and malignant cells

E-cadherin tumor suppressor genes are particularly active area of research in development and tumorigenesis. The calcium-dependent interactions among E-cadherin molecules are critical for the formation and maintenance of adherent junctions in areas of epithelial cell-cell contact. Loss of E-cadherin-mediated-adhesion characterises the transition from benign lesions to invasive, metastatic cancer. Nevertheless, there is evidence that E-cadherins may also play a role in the wnt signal transduction pathway, together with other key molecules involved in it, such as beta-catenins and adenomatous poliposis coli gene products. The structure and function of E-cadherin, gene and protein, in normal as well as in tumor cells are reviewed in this paper

Wnt signal transduction pathway and apoptosis: a review

The association between the wnt signaling pathway and apoptosis has become more firmly established in the recent scientific literature. Many reports indicate that the wnt signaling pathway regulates apoptosis through a variety of mechanisms

Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling.

Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO). However, up to 20% histologically classified as atypical (grade II) or anaplastic (grade III) are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed

Gubitak heterozigotnosti gena APC u slučaju vestibularnog švanoma procijenjen dvama intragenskim biljezima

Schwannomas are benign encapsulated tumors of Schwann cells, the main peripheral glia cells. The majority of schwannomas arise spontaneously and account for 8% of intracranial tumors. Those involving the cerebellopontine angle are schwannomas in 90% of cases. A case is presented of the loss of heterozygosity of the adenomatous polyposis coli (APC) gene in a female patient with cranial schwannoma from Croatia. The observed change of the APC gene was investigated by use of two intragenetic markers. In the light of novel findings on merlin connection to the wnt signaling reported in the literature, the finding of gross deletion in a patient with cranial vestibular schwannoma is a relevant genetic event.Švanomi (neurinomi, neurilemomi) su dobroćudni tumori podrijetlom od Schwannovih stanica, glavnih perifernih glia stanica. Većina švanoma javlja se spontano, tj. sporadično u populaciji, a pojavnost im iznosi 8% ukupnog broja intrakranijskih tumora. Tumori smješteni u pontocerebelarnom kutu su u 90% slučajeva upravo švanomi. U ovom radu prikazan je nalaz gubitka heterozigotnosti gena APC (adenomatous polyposis coli) u bolesnice sa švanomom iz Hrvatske. Velika delecija gena APC istražena je i dokazana uporabom dvaju intragenskih biljega. U svjetlu novih spoznaja o vezi merlina, produkta gena NF 2, i signalnog puta wnt čiji je APC sudionik, opisani nalaz o gubitku heterozigotnosti predstavlja vrijedan doprinos genetičkom profilu švanoma

Disekantni osteohondritis na koljenu adolescenta iz starohrvatskoga groblja Gluvine kuće (deveto stoljeće n.e.)

Although osteochondritis dissecans of the knee has been known for a long time, we still do not fully understand why it develops. This prompted us to present and describe an example of osteochondritis dissecans identified in the Osteological Collection of the Croatian Academy of Sciences and Arts. The case of osteochondritis dissecans described in this report was recovered from the Gluvine kuće cemetery in the Dalmatian hinterland, approximately 28 km north-east of Split. A total of 77 graves were excavated and the individual exhibiting osteochondritis dissecans was recovered from grave number 16 that belongs to the younger phase of the cemetery that lasted during the second half of the 9th century A.D. Osteochondritis dissecans was noted in a subadult individual. The pathological changes consistent with osteochondritis dissecans are present on both medial femoral condyles. The lesion on the right femoral condyle is an oval crater-like defect with well defined margins and a porous floor of rough trabecular bone. The lesion on the left femoral condyle is basically, with two small provisions, identical to the one on the right side. The first is that it is slightly smaller, while the second is that unlike its antimere, it has a well preserved bone fragment that fits perfectly into the ostechondritic pit. Radiographic analyses of the femoral condyles support a diagnosis of osteochondritis dissecans and show a well-demarcated radiolucent defect in the articular surfaces of both joints surrounded by a thin sclerotic repair zone. According to the classification systems this degree of change corresponds to stage 3 or grade 3 osteochondritis dissecans – a detached but non-displaced fragment. Returning, for a second, to the opinion that prompted us to present this case, it is clear that during the last 1100 years there have been no significant morphological or radiological changes in the characteristics of osteochondritis dissecans.Disekantni osteohondritis, osobito onaj u području femoralnih kondila, poznat je stoljećima, ali se još uvijek raspravlja o uzrocima njegova nastanka. To nas je potaknulo da prikažemo slučaj osteohondritisa u području kondila femura iz Osteološke zbirke Zavoda za arheologiju Hrvatske akademije znanosti i umjetnosti. Kostur na kojem je nađen disekantni osteohondritis otkopan je na arheološkom nalazištu Gluvine kuće u Dalmatinskom zaleđu oko 28 kilometara sjeveroistočno od Splita. Na nalazištu je ukupno otkopano 77 grobova, a kostur s patološkim nalazom nađen je u grobu broj 16 koji se vremenski datira u drugu polovinu 9. stoljeća poslije Krista. Disekantni osteohondritis je nađen na kosturu osobe koja je u trenutku smrti imala 13,5 do 15 godina. Kostur je dobro očuvan, sa svijetlo smeđim kostima čiji je korteks imao relativno malo post-mortalnih oštećenja. Patološke promjene u smislu nalaza disekantnog osteohondritisa prisutne su na medijalnim kondilima obaju koljena. Lezija na desnom medijalnom kondilu femura imala je jasno omeđene rubove, a dno mu je činila gruba trabekularna kost. Gotovo jednaka lezija nađena je i na lijevom medijalnom kondilu, samo što je ova bila nešto manjeg promjera i, što je naročito zanimljivo, posjedovala je slobodni fragment kosti koji je točno odgovarao defektu na kondilu femura. Radiografska analiza medijalnih kondila obaju femura pokazala je karakterističnu radiolucentnu demarkacijsku liniju na zglobnoj ploštini obaju kondila okruženu sklerotičnom zonom kosti, što je tipičan radiološki nalaz kao i kod današnjih nativnih rendgenograma. U skladu s postojećim klasifikacijama u stupnjeve patoloških promjena pri postojanju disekantnog osteohondritisa u prikazanom slučaju radilo se o 3. stupnju, tj. stupnju s demarkiranim fragmentom. Na temelju našeg prikazanog slučaja može se zaključiti da u proteklih 1100 godina nije došlo do morfoloških i radioloških promjena u slici disekantnog osteohondritisa u području koljena

Brain metastases from lung cancer show increased expression of DVL1, DVL3 and beta-catenin and down-regulation of E-cadherin

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