Neoexpression of N-cadherin in E-cadherin positive colon cancers.
In our study, we aimed to investigate the expression of N-cadherin and E-cadherin and their dependency on epithelial-mesenchymal transition regulators SNAI1, SIP1 and TWIST in human colon cancer. Expression of E-cadherin and N-cadherin was examined by immunohistochemistry in 80 colon carcinomas by using paraffin embedded and formalin fixed tissues. Those cases were partly analyzed for mRNA expression of N-cadherin (42 cases), TWIST (18 cases), SNAI1 (25 cases) and SIP1 (25 cases) by real-time quantitative RT-PCR. Additionally, colon carcinomas that showed amplification of 20q13, the localization of the human SNAI1 gene, were examined. We found cytoplasmic and/or membrane-associated immunoreactivity of N-cadherin in 35/80 (44%) of the cases. However, there was no correlation to upregulated TWIST mRNA levels, as we have shown previously for diffuse-type gastric cancers with abnormal N-cadherin expression. Reduced and/or cytoplasmic E-cadherin immunoreactivity was detected in 19% (15/80) of the cases. Expression of SNAI1 or SIP1 mRNA was not seen in any of the 25 cases analyzed. There was no correlation between amplification of 20q13 and SNAI1 mRNA expression. Remarkably, N-cadherin was almost exclusively expressed in those cases showing normal E-cadherin immunoreactivity, suggesting a mutual exclusion between abnormal E-cadherin reduction and upregulation of N-cadherin. For the first time, we postulate a role for N-cadherin in primary colon cancer progression, which may be similar to the effect discovered by others in breast cancer cell lines, where coexpressed N-cadherin can exert a dominant function over E-cadherin's adhesive function and thus promote tumor invasiveness.
Rosivatz
Erika
E
Institut für Pathologie der TU, München, Germany.
Becker
Ingrid
I
Bamba
Masamichi
M
Schott
Christina
C
Diebold
Joachim
J
Mayr
Doris
D
Höfler
Heinz
H
Becker
Karl-Friedrich
KF
D000230:Adenocarcinoma / Q000235:genetics* / Q000503:physiopathology*; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D003593:Cytoplasm; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000494:pharmacology; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000494:pharmacology; D051879:Twist-Related Protein 1
D015820:Cadherins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D012313:RNA