High Pin1 expression is associated with tumor progression in colorectal cancer.
OBJECTIVE
Peptidyl prolyl cis-trans isomerase (Pin1) isomerizes only phosphorylated serine or threonine residues preceding proline in certain proteins and affects the protein function. Pin1 interacts with many signaling pathways, including Wnt signaling pathway that is crucial for colorectal tumorigenesis. Pin1 promotes cyclin D1 over-expression directly or through the stabilization of beta-catenin. Pin1 is over-expressed in some cancers such as prostate and breast cancers. This study aimed to determine whether Pin1 plays a role in colorectal tumorigenesis through the upregulation of beta-catenin and cyclin D1.


METHODS
Immunohistochemical analyses were performed on 105 colorectal cancer tissue samples using anti-Pin1, anti-beta-catenin, and anti-cyclin D1 antibodies. We examined the relationships between Pin1 expression and clinicopathological factors, prognosis, and beta-catenin/cyclin D1 expression.


RESULTS
High Pin1 expression was observed in 40 cases (38%) and positively correlated with histological type (P=0.0240), depth of invasion (P=0.0051), and staging (P=0.0027) of colorectal tumors. High Pin1 expression was also correlated with the over-expressions of both beta-catenin (P=0.0225) and cyclin D1 (P=0.0137).


CONCLUSIONS
These results suggest that Pin1 plays an important role in colorectal tumorigenesis, presumably by increasing beta-catenin and cyclin D1 expressions.
Kuramochi
Junichi
J
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. kuramochi.srg2@tmd.ac.jp
Arai
Takehiro
T
Ikeda
Satoshi
S
Kumagai
Jiro
J
Uetake
Hiroyuki
H
Sugihara
Kenichi
K
D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D019696:Peptidylprolyl Isomerase / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D015996:Survival Rate; D051176:beta Catenin / Q000378:metabolism*
D051176:beta Catenin; D019938:Cyclin D1; D019696:Peptidylprolyl Isomerase