Abstract
IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.
Highlights
The insulin-like growth factor (IGF) signaling pathway has an important role in cell growth, differentiation, apoptosis regulation and tumor development [1]
Some studies concluded that IGFBP5 acts as an oncogene, since the high protein level is linked to proliferation, metastasis, poor prognosis, drug sensitivity and limited response to endocrine treatment, but on the other hand some studies revealed that IGFBP5 acts as a tumor suppressor gene due to being related with apoptotic, anti-metastatic, and anti-migratory effects and good outcomes [1]
We did not find a statistically significant increase in IGFBP5 in breast cancer tissues compared to adjacent normal tissue, but higher expression of IGFBP5 was correlated with advanced tumor grades (p = 0.0123)
Summary
The insulin-like growth factor (IGF) signaling pathway has an important role in cell growth, differentiation, apoptosis regulation and tumor development [1]. The IGF axis comprises two growth factors (IGF-I, IGF-II), two IGF receptors (IGF-IR, IGF-IIR), and seven IGF-binding proteins (IGFBPs) which regulate the mitogenic activities of the IGFs, a group of IGFBP-related proteins that bind IGFs with low affinity and IGFBP proteases. Some studies concluded that IGFBP5 acts as an oncogene, since the high protein level is linked to proliferation, metastasis, poor prognosis, drug sensitivity and limited response to endocrine treatment, but on the other hand some studies revealed that IGFBP5 acts as a tumor suppressor gene due to being related with apoptotic, anti-metastatic, and anti-migratory effects and good outcomes [1]
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