title: Expression of tight junction molecules in breast carcinomas analysed by array PCR and immunohistochemistry.
abstract: In the past few decades an enormous amount of data became known to clarify the molecular composition and architecture of tight junctions (TJs). Despite the efforts, the expression and function of several TJ genes and proteins in breast carcinoma are still not known and some of the data are contradictory. The expression of forty-four TJ associated genes was examined at mRNA level in eighteen invasive ductal breast carcinoma samples and corresponding normal breast tissues by using low density array PCR. Expressions of claudins (CLDNs) 5, 10, 16, 17, and 18, and ZO-1, ZO-2 were evaluated by immunohistochemistry as well. Using immunohistochemical phenotype as a surrogate for the genetic subtype, 11 luminal A, 3 luminal B, 3 triple negative and one HER2+ cases were included. Ten genes were significantly downregulated in tumors compared with normal breast tissues (CLDNs 5, 10, 16, 18, 19, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3), whereas one gene (CLDN17) was significantly up-regulated in tumors when compared with normal breast. At protein level CLDNs 5, 10, 16, 18, ZO-1 and ZO-2 were downregulated in tumors as compared with normal breast tissue. CLDN17 showed variable expression in tumor tissues in comparison to normal breast. In the single HER2+ tumor when compared with the other subtypes CLDNs 5, 16, 17, 18, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3 genes were found to be upregulated. We found altered TJ genes and proteins whose expression has not yet been associated with breast carcinoma. Our findings show a tendency of TJ genes and proteins to be downregulated in breast cancer. Further studies are necessary to examine whether the downregulation of the above mentioned TJ associated genes and proteins may contribute to the malignant progression of invasive ductal breast carcinomas.
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Ulloi ut 93, 1091 Budapest, Hungary. tokesa1972@yahoo.co.uk
authors.forename: Anna-Mária
authors.initials: AM
authors.lastname: Tőkés
authors.forename: Attila Marcell
authors.initials: AM
authors.lastname: Szász
authors.forename: Eva
authors.initials: E
authors.lastname: Juhász
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Schaff
authors.forename: László
authors.initials: L
authors.lastname: Harsányi
authors.forename: István Arthur
authors.initials: IA
authors.lastname: Molnár
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Baranyai
authors.forename: István
authors.initials: I
authors.lastname: Besznyák
authors.forename: Attila
authors.initials: A
authors.lastname: Zaránd
authors.forename: Ferenc
authors.initials: F
authors.lastname: Salamon
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases