Stage-specific alternative cplicing of CD44 and alpha 6 beta 1 integrin in colorectal tumorigenesis.
Recent reports suggest that cancerogenesis induces changes in alternative processing of human genes. However, little is known about the regulation of alternative splicing during malignant transformation. Therefore, we examined changes in alternative splicing of two different adhesion molecules, alpha 6 beta 1 integrin and CD44, in multiple stages of colon tumorigenesis. Using semiquantitative RT-PCR it is shown that the alternatively spliced isoforms of both adhesion molecules, alpha 6A and -B and CD44v6, are significantly upregulated in colorectal adenoma (n = 20) compared to normal colon mucosa (n = 32) (P < 0.01). Although beta1 isoforms were expressed in almost all tissues, there was a significant increase in the intensity of gene expression of beta 1A compared to beta 1B (P <0.05) in adenoma tissue. Interestingly, CD44v6 and alpha 6 variant isoforms were downregulated in carcinoma tissue (n = 28) compared to adenoma. These results establish a link between neoplastic transformation and alternative splicing of cell adhesion molecules. Furthermore, these data suggest that colon epithelial cells carrying splice variants of adhesion molecules might acquire a selective growth advantage during early tumorigenesis.
Department of Internal Medicine II, Saarland University, Homburg/Saar, Germany.
B M
BM
Wittig
R
R
Goebel
S
S
Weg-Remers
G
G
Pistorius
G
G
Feifel
M
M
Zeitz
A
A
Stallmach
D000230:Adenocarcinoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D017398:Alternative Splicing; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003106:Colon / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics*; D039121:Integrin alpha6beta1; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018960:Hyaluronan Receptors; D039121:Integrin alpha6beta1; D016023:Integrins