Identification of a putative tumor suppressor gene,CDH10, in colorectal cancer
Date Issued
2009
Date
2009
Author(s)
Lai, Yen-Chun
Abstract
Colorectal cancer (CRC) is one of the most common malignancies and is the third leading cause of cancer death in Taiwan. Three major pathways, loss of heterozygosity, microsatellite instability and epigenetic regulation are demonstrated in CRC tumorigenesis. To identify putative tumor suppressor genes associated with CRC, deletion mapping on chromosome 4 was performed by loss of heterozygosity analysis with colorectal cancer paired tissues. Previous data figured out that expression of PCDH10 variant 1 is significantly down-regulated in tumor tissues than their paired normal mucosa. On the other hand, the expression of PCDH10 is regulated by epigenetic modification. These data support that PCDH10 might be a putative tumor suppressor gene associated with in colorectal cancer. It has been reported that PCDH10 gene is transcribed into 2 kinds of mRNA variants. In the present study, PCDH10 mammalian expression vectors were constructed and over-expressed in colorectal cancer cell line, HCT116, and then the cells were analyzed by functional assays. The results showed transient over-expression of PCDH10 variant 1 could suppress cell proliferation and invasion, while over-expression of PCDH10 variant 2 only inhibited cell proliferation. Furthermore, we got two of PCDH10 variant 1 single stable clones and one of PCDH10 variant 2. PCDH10 variant 1 single stable clones could repress cell growth and colony formation in protein expression level-dependent manner. There is no same effect in PCDH10 variant 2 stable expression clone. Moreover, through construction of PCDH10-GFP fusion protein vector and immunofluorecent stain of theCDH10 variant 1 single stable clone, we identified the localization of PCDH10 protein in cells. Both PCDH10 variant 1 and variant 2 were expressed on cell membrane and seemed to be co-localizated. In conclusion, PCDH10 variant 1 can suppress cell proliferation and invasion in HCT116, suggesting that PCDH10 variant 1 might be a putative tumor suppressor gene associated with colorectal tumorigenesis.
Subjects
colorectal cancer
tumor suppressor gene
SDGs
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