| First Author | Bigsby RM | Year | 2011 |
| Journal | Carcinogenesis | Volume | 32 |
| Issue | 8 | Pages | 1162-6 |
| PubMed ID | 21606321 | Mgi Jnum | J:174984 |
| Mgi Id | MGI:5141587 | Doi | 10.1093/carcin/bgr094 |
| Citation | Bigsby RM, et al. (2011) The role for estrogen receptor-alpha and prolactin receptor in sex-dependent DEN-induced liver tumorigenesis. Carcinogenesis 32(8):1162-6 |
| abstractText | Mice treated neonatally with diethylnitrosamine (DEN) develop liver tumors in a male-dominant manner, reflecting the male bias in human hepatocellular carcinoma. Evidence suggests that estrogen, androgen, prolactin (PRL) and growth hormone (GH) modify liver tumorigenesis. We determined the roles of estrogen receptor-alpha (ERalpha) and prolactin receptor (PRLR) using receptor null mice, ERalphaKO (C57Bl/6J) and PRLR-KO (129Ola-X-C57BL/6), in the neonatal-DEN model of liver tumorigenesis. In both mouse strains, females had reduced tumorigenesis compared with males (P < 0.01), regardless of ERalpha or PRLR status. Tumorigenesis was not affected by ovariectomy in C57Bl/6J mice but it was increased by ovariectomy in the mixed strain, 129Ola-X-C57BL/6, regardless of PRLR status. ERalphaKO males had 47% fewer tumors than ERalpha wild-type males (P < 0.01). On the other hand, estradiol treatment protected against tumorigenesis in males only in the presence of ERalpha. As evidenced by liver gene expression, lack of ERalpha did not alter the pattern of GH secretion in males but resulted in the male GH pattern in females. These observations indicate that ERalpha is not required for lower tumorigenesis in females, but it is required for the protective effects of exogenously delivered estradiol. Unexpectedly, the results indicate that ERalpha plays a role in promotion of liver tumors in males. In addition, it can be concluded that sex differences in liver tumorigenesis cannot be explained by the sexually dimorphic pattern of GH secretion. The results also rule out PRL as the mediator of the protective effect of the ovaries. |
