Cancer Genetics and Epigenetics 2018, Vol.6, No.4, 25-32
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3.3 Free IGF2 level and breast cancer
This study investigated the relationship between IGF2 and breast cancer. In the circulatory system of patients with
limited and early breast cancer, the level of free IGF1/IGF2 increased significantly, the level of total IGF2
decreased, and the level of IGBPs changed. Despite the low incidence, it can be seen that IGF system plays a role
in disease progression. IGF2 receptors have a high affinity with IGF2, which can eradicate other growth factors
and reduce extracellular IGF2 levels. Studies on breast cancer tissues showed that the expression of IGF2 was
increased. In the transition zone between normal epithelium and tumor tissues, stromal cells and leukocytes
expressed IGF2, which might stimulate lymphocyte formation. Therefore, the level of IGF2 in extracellular
environment was closely related to tumorigenicity. The addition of IGF2 in cancer tissues could stimulate cell
proliferation, while the expression of IGF2 receptor transfected cancer cells. Inhibiting its growth and increasing
apoptosis. Studies have shown that circulating free IGF2 levels are correlated with breast cancer size, but
paradoxically, the level of circulating free IGF2 in cancer patients is lower than that in the control group. It is
noteworthy that these findings become apparent only after correcting changes in body fluid composition after
surgery. The serum level of IGFBP2 in cancer patients is lower than that in control group. This binding protein is
an important determinant of free IGF2 level. Lower IGFBP2 may increase the free fraction of IGF2. This
experiment concluded that free IGF2 may respond to the increase of biological activity of this axis in women with
breast cancer, confirming that the production of IGF2 in breast cancer can promote local growth and increase the
anti-apoptotic signal (Espelund et al., 2008).
3.4 IGF2 and breast cancer susceptibility in special population
The experiment compared that African-American (AA) women with breast cancer were more likely than
Caucasian (CA) women to change for advanced diseases, with higher risk of recurrence and worse prognosis. The
expression of IGF2 in paired breast tissue samples was higher in AA women than in CA women. IGF2 can induce
strong mitogen of cell proliferation and survival signal by activating IGF1 and IGF1R (IGF1 receptor). The level
of IGF2 cycle is regulated by cell uptake of IGF2R. IGF2R plays a role in maintaining the level of IGF2 in target
tissue. Overexpression of IGF2 in MCF-7 breast cancer cells can increase the secretion of lysosomal cathepsin D.
Its secretion and prognosis are poor and metastasis increase phase. It can also reduce the disease-free survival of
breast cancer patients. The expression of IGF1R in normal AA tissues was significantly higher than that in normal
CA tissues. The expression of IGF1R in normal AA tissues was similar to that in malignant AA tissues. It was
concluded that the difference in the expression of IGF1R and IGF2R might increase the risk of malignant
transformation of breast in young AA women and contribute to the more aggressive phenotype of breast cancer
(Kalla et al., 2010; Dong et al., 2015).
The lifetime risk of breast cancer in BRCA1 and BRCA2 gene mutation carriers is 40%-80%, indicating that there
is a risk modifier (Xu et al., 2016). Previous studies have shown that there is an important correlation between
IGF signaling pathway and gene mutation. In this study, whether the additional IGF signaling gene can be used as
a risk regulator for breast cancer in BRCA gene carriers. Through screening, we focused on 13 genes that are
significantly associated with the risk of breast cancer, including IGF1 receptor ligand IGF2 and insulin, IGF
binding protein and so on. This study confirmed that IGF2 is a risk regulator (Neuhausen, 2011) associated with
breast cancer in BRAC1 and BRCA2 mutations.
4 Outlook
In conclusion, the abnormal activation of IGF2 signaling pathway, the hypomethylation of IGF2 gene and the
increase of peripheral free IGF2 level can promote the growth, transcription and expression of breast cancer cells,
suggesting that IGF2 gene has potential for diagnosis and prediction of breast cancer. The whole process is
accomplished by affecting multiple signal transduction pathways. Therefore, it is of great significance to study the
clinical application value and mechanism of IGF2 in breast cancer treatment, promote the development of breast
cancer treatment and develop safe and effective anti-cancer drugs.
