Biochemically, they had elevated total IGF-1, IGFBP-3, IGFBP-5, acid labile subunit and IGF-2 levels, most of which are GH-dependent factors.
The homozygous Pappa2 KO animals had increased IGFBP-5 levels and variable levels of IGFBP-3 compared with WT (21,22).
The genes to be predicted (i.e., targets) were selected on the basis of biological relevance and included Ahr, Cyp1b1, Igfbp-5, Lox, and Opn.
Igfbp-5 was most frequently predicted by Opn (14%), matrix metalloproteinase 3 (9%), and RNA binding motif-single-stranded interacting protein 1 (8%).
"IGFBP-2 and IGFBP-5 are exciting drug targets as they facilitate access to a key alternate growth factor which enables tumors to progress in the absence of hormone.
The expansion combines OncoGenex's leading patent position in inhibitors of IGFBP-5 and IGFBP-2 drug targets with Isis' second-generation antisense chemistry, called 2'-O-methoxyethyl, as well as Isis' IGFBP-5 target-specific intellectual property.
IGFBP-5 expression was relatively constant throughout development.
IGF-II (E16-P42), IGF-IR (E18-P42), IGFBP-2 (E18-P42), IGFBP-5 (E16-P14), IGFBP-7 (E12-P0), and IGFBP-3 (E12-P0) were positively correlated with IGF-I, while IGFBP-3 (P0-P28) was negatively correlated with IGF-I.
On the other hand, IGFBP-3 and IGFBP-5 are much lower in older individuals than younger ones (34).
Evidence that human bone cells in culture produce IGFBP-4 and IGFBP-5 proteases.
In postnatal life, IGF-I and -II circulate as 150 kDa ternary complexes consisting of one molecule each of IGFBP-3 or IGFBP-5, IGF-I orIGF-II and ALS.
This complex consists of one molecule each of IGF-I or IGF-II, IGF-binding protein (IGFBP)-3 or IGFBP-5 and an acid labile subunit (ALS).