Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice.
OBJECTIVE
To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the contribution of adiponectin deficiency to colorectal cancer development and proliferation.


METHODS
We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, intraperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice.


RESULTS
At 53 wk after the first AOM treatment, KO mice developed larger and histologically more progressive colorectal tumors with greater frequency compared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorectal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOM treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of KO mice developed liver tumors, and 58% of these KO mice had multiple tumors.


CONCLUSIONS
Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.
Nishihara
Tamao
T
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. tamaon@gh.med.osaka-u.ac.jp
Baba
Miyako
M
Matsuda
Morihiro
M
Inoue
Masahiro
M
Nishizawa
Yasuko
Y
Fukuhara
Atsunori
A
Araki
Hiroshi
H
Kihara
Shinji
S
Funahashi
Tohru
T
Tamura
Shinji
S
Hayashi
Norio
N
Iishi
Hiroyasu
H
Shimomura
Iichiro
I
D052242:Adiponectin / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001397:Azoxymethane; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D052242:Adiponectin; C499919:Adipoq protein, mouse; D018809:Proliferating Cell Nuclear Antigen; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001397:Azoxymethane