Wnt signaling may be activated in a subset of Peutz-Jeghers syndrome polyps closely correlating to LKB1 expression.
The premalignant potential of Peutz-Jeghers syndrome (PJS) hamartomas has not been established. The major gene responsible for PJS is LKB1. LKB1 has a complex cellular role, therefore, the exact role of LKB1 in Peutz-Jeghers syndrome hamartomas (PJSs) is particularly difficult to understand. It has recently been found that LKB1 functions in the Wnt pathway in Xenopus during early development. Aberrant beta-catenin expression, the key regulator of the activated Wnt/beta-catenin signaling pathway, appears to stimulate interferon-induced gene 1 (IFITM1) products in intestinal tumorigenesis. Both contribute to intestinal tumor formation and tumor progression. This study was designed to investigate expression of LKB1, beta-catenin and IFITM1 in PJSs, colorectal adenomas (CRAs), colorectal carcinomas (CRCs) and normal colorectal mucosas (NCs) using RT-PCR and immunohistochemistry. Immunofluorescence was used to assess the co-expression characteristics of beta-catenin and IFITM1. Results showed that the expression profiles of LKB1, beta-catenin and IFITM1 in PJSs were similar to those in CRAs both at the mRNA and protein levels. The cytoplasmic level of beta-catenin expression correlated strongly with LKB1 and IFITM1 expression in the tumor cells. The dyregulation of beta-catenin was found in a majority (16/20) of the PJS polyps. Immunofluorescence also revealed co-expression of beta-catenin and IFITM1 in the cytoplasm of the PJSs. These findings suggest that Wnt signaling may be activated in a subset of PJSs, and activation of the Wnt/beta-catenin signaling in PJS polyps may be caused by LKB1 expression. The activated beta-catenin signaling pathway including IFITM1 might play an important role in a subset of PJS polyps.
Ma
Yamei
Y
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Zhang
Guohua
G
Fu
Xiangsheng
X
Xia
Oudong
O
Zhan
Chunling
C
Li
Lianjie
L
Wang
Zhiqing
Z
Wu
Baoping
B
D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000943:Antigens, Differentiation; D015153:Blotting, Western; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010580:Peutz-Jeghers Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D000943:Antigens, Differentiation; D008565:Membrane Proteins; D012333:RNA, Messenger; D051176:beta Catenin; C062010:leu-13 antigen; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases