Further in vivo studies demonstrated that the stable overexpression of miR-663b or knock-down of HOTAIR inhibited tumor growth and was associated with IGF2 expression.
This study supports the concept of direct autocrine/paracrine tumor cell activation through IGF2 and a shows role of IGF2 in CRC proliferation, adhesion and, to a limited extent, apoptosis.
Lastly, the expression of HMGA1P7 was significantly correlated with H19 and IGF2 levels in human breast cancer thereby suggesting a role for HMGA1P7 deregulation in this neoplasia.
To test the tumorigenic potential of different cell types in the developing kidney, we used kidney progenitor-specific Cre recombinase alleles to introduce Wt1 and Ctnnb1 mutations, two alterations observed in Wilms tumor, into embryonic mouse kidney, with and without biallelic Igf2 expression, another alteration that is observed in a majority of tumors.
Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%).
Loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) is thought to be implicated in the pathogenesis of some tumors by upregulating IGF2 mRNA but its role in the pathogenesis of fibroadenomas (FAs) and phyllodes tumors (PTs) of the breast is yet to be studied.
Mice with xenograft tumors grown from HCC cells were given a monoclonal antibody against IGF1 and IGF2 (xentuzumab), along with sorafenib; tumor growth was measured and tissues were analyzed by immunohistochemistry and immunoblots.
Therefore, the results demonstrated that the lncRNA 91H was associated with H19 ICR methylation and inhibited IGF2 expression of ESCC patients which may optimize the mechanism of IGF2 regulation in tumor development.
Some studies have also reported on qualitative immunohistochemical analysis of tumor tissue, in particular with respect to the expression of IGF-II at the mRNA or protein level.
We demonstrate that IGF2 expression in IH is strongly related to the expression of a cancer testes and suspected oncogene BORIS (paralog of CTCF), placing IH in the unique category of being the first known benign BORIS positive tumor.
Studies examining rare genetic syndromes responsible for familial ACT have played an important role in identifying genetic alterations in these tumors (like TP53 or CTNNB1 mutations as well as IGF2 overexpression).
Furthermore, miR-216b downregulated the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and exerted its tumor-suppressor function through inhibition of protein kinase B and extracellular signal-regulated kinase signaling downstream of IGF2.
While intense efforts are being made to explore the genetic basis of the other two-thirds of tumor cases, it is worth noting that, epigenetic changes, particularly the loss of imprinting of the DNA region encoding the major fetal growth factor IGF2, which results in its biallelic over-expression, are closely associated with the development of many Wilms tumors.
Finally, analysis of the 11p15 locus showed a paternal uniparental disomy in both IGF2-high and IGF2-low tumors, but low IGF2 expression could be explained in most IGF2-low ACC by an additional epigenetic modification at the 11p15 locus.
With the use of a molecular pathologic epidemiology database in 2 prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association between alcohol intake and incident colorectal cancer according to the tumor methylation level of IGF2 DMR0.
Moreover, assessment of tumor expression of IGF-II, phospho-IGF-IR, or PTEN status may help select patients with ovarian cancer who are most likely to benefit from ganitumab.
As a consequence, the expression of IGF1R and IGF2 was found in human OS with higher strong reactivity rate compared with the NTT (85.0 percent vs 50.0 percent, P=0.022; 95.0 percent vs 100.0 percent, P=0.042), elevating with the ascending order of tumor malignancy.