Insulin-like growth factor-I (IGF-I) is a single-polypeptide chain cytokine involved in tissue growth and differentiation. We hypothesized that altered IGF-I receptor expression in conjunction with changes in IGF-I production may be a key factor in the development and/or progression of experimental HCC. Tumorigenic H4IIE hepatoma cells were inoculated into the right hepatic lobe of ACI rats resulting in reproducible parenchymal tumor growths 14 days post-inoculation. Circulating levels of GH and IGF-I were determined in serum at 2 day intervals post-inoculation (day 2 to day 14) using RIA's. These data demonstrated no significant changes in circulating GH or IGF-I levels throughout the duration of HCC development (n=5). Cell fractions were prepared from right and left hepatic lobes of both tumor bearing and sham operated (saline vehicle only) animals 14 days post-inoculation. Western blot analysis was then performed using a polyclonal antibody raised against the IGF-I receptor that detects both a 130kDa protein (receptor α-subunit), and a second 180kDa protein (receptor pro-α-subunit). Both the α-subunit and the pro-α-subunit protein were significantly elevated in non-tumor bearing lobes (NT) as compared to tumor (T) and sham operated (Sh) membranes (246±24% and 141±14% respectively, n=5, p<0.05). No significant differences were observed between sham operated and tumor tissue. Northern blot analysis demonstrated significantly elevated levels of IGF-I mRNA in NT as compared to sham operated animals (312±34%, n=4, p<0.05). Northern blot analysis of tumor samples indicated no detectable expression of IGF-I mRNA (n=4). These data suggest an increased intra-hepatic role for IGF-1 in the absence of altered circulating levels of either IGF-I or GH in HCC. Furthermore the absence of IGF-I mRNA in tumorigenic tissue suggests that IGF-I is produced in response to tumor burden by non-tumorigenic liver in a paracrine/autocrine manner and may play an integral role in the maintenance of organ function and adaptation during HCC development.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology