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Genetic background determines if Stat5b suppresses or enhances murine hepatocarcinogenesis
Author(s) -
Oberley Christopher C.,
Bilger Andrea,
Drinkwater Norman R.
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22165
Subject(s) - biology , congenic , null allele , allele , gene , cancer research , oncogene , stat protein , endocrinology , medicine , genetics , cell cycle , stat3
Murine hepatocarcinogenesis requires growth hormone (GH). To determine if the GH‐responsive transcription factor STAT5b (signal transducer and activator of transcription 5b) is also required, we compared the hepatic gene expression profiles of global Stat5b null mice to cancer‐resistant mice mutant in the GH pathway—GH‐deficient little and androgen receptor‐null Tfm males. We found a high degree of overlap among Tfm , little , and Stat5b null males. The liver cancer susceptibility of global Stat5b null mice was assessed on three distinct genetic backgrounds: BALB/cJ (BALB), C57BL/6J (B6), and C3H/HeJ (C3H). The effect of Stat5b on hepatocarcinogenesis depended on the genetic background. B6 Stat5b null congenic males and females developed 2.4 times as many tumors as wild‐type (WT) controls ( P < 0.002) and the tumors were larger ( P < 0.003). In BALB/c congenics, loss of STAT5b had no effect on either sex. C3H Stat5b null congenic males and females were resistant to liver cancer, developing 2.7‐ and 6‐fold fewer tumors, respectively ( P < 0.02, 0.01). These results provide the first example of a single gene behaving as both oncogene and tumor suppressor in a given tissue, depending only on the endogenous modifier alleles carried by different genetic backgrounds. © 2014 Wiley Periodicals, Inc.