Extremely weak tumor-promoting effect of troglitazone on splenic hemangiosarcomas in rasH2 mice induced by urethane.
To examine the tumor-promoting effect of troglitazone (TRG), a novel thiazolidinedione insulin-sensitizing agent, on splenic hemangiosarcomas in rasH2 mice, histopathological and molecular analyses were performed in the spleen of female rasH2 mice fed a diet containing 6,000 or 0 ppm TRG for 16 weeks after 1,000 or 0 mg/kg urethane (UR) initiation. Histopathologically, splenic hemangiosarcomas were observed in the UR-alone and UR + TRG groups, but there was no significant difference in the incidence of splenic hemangiosarcomas between the UR-alone and UR+TRG groups. There were increasing tendencies in the number of positive cells for anti-PCNA antibody and gene expression in the UR + TRG group, but such a change was not statistically significant as compared to that in the UR-alone group. The gene expressions of VEGF, VEGFR1, VEGFC, VEGFR2 and Tie2 related to angiogenesis; c-fos related to MAPK cascade activation; and cyclin D1 related to cell cycle in the UR-alone and UR + TRG groups were significantly higher than those in the untreated control group. However, only the Tie2 gene in the UR + TRG group was significantly increased as compared to that in the UR-alone group. These results suggest that the vascular tumor-promoting activity of TRG in rasH2 mice is extremely low in the present experimental condition and a part of the gene related to angiogenesis probably contributes to the promotion of splenic hemangiosarcomas in rasH2 mice given TRG.
Jin
Meilan
M
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan. meilan@cc.tuat.ac.jp
Matsumoto
Sayaka
S
Dewa
Yasuaki
Y
Nishimura
Jihei
J
Saekusa
Yukie
Y
Hasumi
Keiji
K
Mitsumori
Kunitoshi
K
D042501:Angiogenic Proteins / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000633:toxicity*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006394:Hemangiosarcoma / Q000098:blood supply / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D013160:Splenic Neoplasms / Q000098:blood supply / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D045162:Thiazolidinediones / Q000633:toxicity*; D013997:Time Factors; D000077288:Troglitazone; D014520:Urethane
D042501:Angiogenic Proteins; D002273:Carcinogens; D002839:Chromans; D045162:Thiazolidinediones; D014520:Urethane; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000077288:Troglitazone