Effect of thyroid hormones on hepatic tumor induced by ras oncogene

OBJECTIVE To investigate the effects of thyroid hormones on ras oncogene induced hepatic tumorigenesis and development.METHORDS The liver tissues and serum samples of 3,5,7,9-month-age non-transgenic and H-ras12 Vtransgenic male mice(48)were collected.The liver/body weight ratio and levels of total and free serum T3,T4 were detected.The mRNA levels of TBG and the protein levels of Cyclin D1 in the liver tissues of 9-month-age nontransgenic and H-ras12 V transgenic male mice were detected by RT-qPCR and Western blot.Thirty-six SPF-grade3-month-age transgenic male mice were randomly divided into control group,hyperthyroidism group(feeding thyroid tablets)and hypothyroidism group(feeding propylthiouracil tablets),12 in each group,and treated for 4months and sampled at 7-month-age.The levels of total serum T3,T4,liver/body weight ratio,and number and size of liver tumors were detected.RESULTS The liver/body weight ratio of 3,5,7,9-month-age transgenic male mice were gradually increased along with aging and significantly higher than that of age-matched non-transgenic male mice(P<0.01).Compared to the non-transgenic male mice,levels of total serum T3,T4 of 9-month-age transgenic male mice increased significantly(P<0.01),but free serum T3,T4 levels had no significant changes.Compared to the liver tissues of 9-month-age non-transgenic male mice and the peri-tumor tissues of transgenic male mice,the mRNA levels of TBG and the protein levels of Cyclin D1 were significantly increased in liver tumor tissues(P<0.01).Compared to the control group,serum T3 and T4levels in hyperthyroid group were increased significantly(P<0.05)and in hypothyroidism group decreased significantly(P<0.05).Compared to the control group,the liver/body weight ratio and total number of liver tumors of hyperthyroid group were decreased significantly(P<0.05).Compared to control group and hypothyroidism group,the number of liver tumors more than 2mm in size in hyperthyroid group was significantly decreased(P<0.05),but there was no significant difference in the number of liver tumors less than 2 mm of size.CONCLUSION Thyroid hormones have significant suppression effects on ras oncogene induced hepatic tumor development,but not tumorigenesis.