The role for estrogen receptor-alpha and prolactin receptor in sex-dependent DEN-induced liver tumorigenesis

Robert Bigsby, Andrea Caperell-Grant

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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-α (ERα) and prolactin receptor (PRLR) using receptor null mice, ERαKO (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 ERα 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. ERαKO males had 47% fewer tumors than ERα wild-type males (P < 0.01). On the other hand, estradiol treatment protected against tumorigenesis in males only in the presence of ERα. As evidenced by liver gene expression, lack of ERα did not alter the pattern of GH secretion in males but resulted in the male GH pattern in females. These observations indicate that ERα 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 ERα 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.

Original languageEnglish
Pages (from-to)1162-1166
Number of pages5
JournalCarcinogenesis
Volume32
Issue number8
DOIs
StatePublished - 2011

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Prolactin Receptors
Diethylnitrosamine
Estrogen Receptor alpha
Carcinogenesis
Estrogen Receptors
Liver
Growth Hormone
Ovariectomy
Prolactin
Estradiol
Neoplasms
Sex Characteristics
Androgens
Hepatocellular Carcinoma
Ovary
Estrogens
Gene Expression

ASJC Scopus subject areas

  • Cancer Research

Cite this

The role for estrogen receptor-alpha and prolactin receptor in sex-dependent DEN-induced liver tumorigenesis. / Bigsby, Robert; Caperell-Grant, Andrea.

In: Carcinogenesis, Vol. 32, No. 8, 2011, p. 1162-1166.

Research output: Contribution to journalArticle

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