Opposing behavioural alterations in male and female transgenic tgfα mice: Association with tumour susceptibility

Psychosocial factors are thought to influence risk and survival from cancer. We have previously studied specific behaviours in transgenic male CD-1 MT42 mice, which overexpress the gene encoding human transforming growth factor α (TGFα) in multiple tissues, and which develop a high incidence of spontaneous hepatocellular carcinoma. The male TGFα mice spent a lengthened time immobile in the swim test, were highly aggressive, had increased plasma levels of 17β-estradiol (E2), and reduced natural killer (NK) cell activity. The female transgenic MT42 TGFα mice do not develop an increased rate of tumours at any site. We hypothesised that if the alterations in male TGFα mice are associated with their development of hepatocellular carcinomas, female TGFα should not show these alterations. The data in the present study indicate that female TGFα mice display shortened immobility in the swim test, suggesting an improved ability to cope with stress, and appear less aggressive in the resident-intruder test than non-transgenic female CD-1 mice. The female TGFα mice also exhibit a 3-fold increase in the plasma levels of E2, and a 3-fold increase in NK cell activity. These findings suggest that the elevated expression of TGFα in the transgenic mice is associated with gender-specific behavioural alterations, and the development of spontaneous hepatocellular tumours in the males. Furthermore, TGFα alters hormonal and immune parameters similarly in both sexes. It remains to be determined whether the development of hepatocarcinoma in the male TGFα animals is associated with an impaired ability to cope with stress and elevated aggressive tendencies and/or whether manipulations leading to an impaired ability to cope with stress will promote tumourigenesis in female TGFα mice.