Overexpression of peptidyl-prolyl isomerase-like 1 is associated with the growth of colon cancer cells.
OBJECTIVE
To discover novel therapeutic targets for colon cancers, we previously surveyed expression patterns among 23,000 genes in colon cancer tissues using a cDNA microarray. Among the genes that were up-regulated in the tumors, we selected for this study peptidyl-prolyl isomerase-like 1 (PPIL1) encoding PPIL1, a cyclophilin-related protein.


RESULTS
Western blot analysis and immunohistochemical staining using PPIL1-specific antibody showed that PPIL1 protein was frequently overexpressed in colon cancer cells compared with noncancerous epithelial cells of the colon mucosa. Colony formation assay showed a growth-promoting effect of wild-type PPIL1 on NIH3T3 and HEK293 cells. Consistently, transfection of short-interfering RNA specific to PPIL1 into SNUC4 and SNUC5 cells effectively reduced expression of the gene and retarded growth of the colon cancer cells. We further identified two PPIL1-interacting proteins, SNW1/SKIP (SKI-binding protein) and stathmin. SNW1/SKIP is involved in the regulation of transcription and mRNA splicing, whereas stathmin is involved in stabilization of microtubules. Therefore, elevated expression of PPIL1 may play an important role in proliferation of cancer cells through the control of SNW1/SKIP and/or stathmin.


CONCLUSIONS
The findings reported here may offer new insight into colonic carcinogenesis and contribute to the development of new molecular strategies for treatment of human colorectal tumors.
Obama
Kazutaka
K
Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Kato
Tatsushi
T
Hasegawa
Suguru
S
Satoh
Seiji
S
Nakamura
Yusuke
Y
Furukawa
Yoichi
Y
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin / Q000378:metabolism
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D050777:Stathmin; C060614:SKI protein, human; D019696:Peptidylprolyl Isomerase