OPPOSING BEHAVIORAL ALTERATIONS IN MALE AND FEMALE TRANSGENIC TGF-ALPHA MICE - ASSOCIATION WITH TUMOR SUSCEPTIBILITY

Psychosocial factors are thought to influence risk and survival from c ancer. We have previously studied specific behaviours in transgenic ma le CD-1 MT42 mice, which overexpress the gene encoding human transform ing growth factor alpha (TGFalpha) in multiple tissues, and which deve lop a high incidence of spontaneous hepatocellular carcinoma. The male TGFalpha mice spent a lengthened time immobile in the swim test, were highly aggressive, had increased plasma levels of 17beta-estradiol (E 2), and reduced natural killer (NK) cell activity. The female transgen ic MT42 TGFalpha mice do not develop an increased rate of tumours at a ny site. We hypothesised that if the alterations in male TGFalpha mice are associated with their development of hepatocellular carcinomas, f emale TGFalpha should not show these alterations. The data in the pres ent study indicate that female TGFalpha mice display shortened immobil ity in the swim test, suggesting an improved ability to cope with stre ss, and appear less aggressive in the resident-intruder test than non- transgenic female CD-1 mice. The female TGFalpha 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 TGFalpha in the transgenic mice is associated with gender-specific be havioural alterations, and the development of spontaneous hepatocellul ar tumours in the males. Furthermore, TGFalpha alters hormonal and imm une parameters similarly in both sexes. It remains to be determined wh ether the development of hepatocarcinoma in the male TGFalpha animals is associated with an impaired ability to cope with stress and elevate d aggressive tendencies and/or whether manipulations leading to an imp aired ability to cope with stress will promote tumourigenesis in femal e TGFalpha mice.