Abstract
Growth factor signaling plays a key role in the growth and development of breast. Aberrant expression and activation of growth factors like insulin like growth factor-I (IGF-I) and epidermal growth factor (EGF) and their downstream signaling has been implicated in breast cancer. The deregulation of growth factor signaling is associated with increased proliferation and cell survival, decreased apoptosis, invasion, angiogenesis and metastasis. The aim of the present study is to survey the different signaling molecules involved in the IGF and EGF signaling pathways, and to find if there are any relationship between breast cancer and their levels and activation. Thirty-nine samples of breast cancer tissues (24 Grade II and 15 Grade III tumours) and sixteen normal breast tissue samples were collected. The expression of the receptors and signaling molecules were investigated using Western blot. IGF-IRβ, AR, pAkt, IKK-α and p38 are upregulated in cancer tissues in a grade depended manner. Further, Akt and β-catenin were also upregulated in cancer samples. Correlation analysis of signaling molecules revealed a disruption in their expression in cancer tissues. The present study shows that various signaling molecules are upregulated or activated in cancer tissues involving IGF-IR and Akt pathway. The expression of signaling molecules in the cancer tissues were deregulated when compared to the control samples. Thus, flawed expression and over activation of Akt pathway is seen in the breast cancer tissues.
Highlights
Breast cancer is a worldwide health concern for women
The distribution of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) statuses is shown in Figures 1(a) and (b)
Correlation analysis within the control and cancer samples show that in normal breast tissues insulin-like growth factor (IGF)-IR has a positive correlation with GSK, β-catenin and ERα, but the correlation between IGF-IR and GSK, and IGF-IR and ERα was lost in cancer tissues indicating a perturbed expression of signaling molecules in cancer cells
Summary
Growth factors stimulate cellular growth, proliferation and differentiation and are vital for the normal development and function of the breast [1]. Insulin-like growth factor (IGF) and epidermal growth factor (EGF) signaling systems are affected leading to abnormal mitogenicity and cell survival. IGF signaling system plays a critical role in the growth and development of many tissues. High serum IGF-I levels predict an increased risk of breast cancer [4]. Both experimental and clinical studies have demonstrated that IGF-IR is overexpressed in cancer cells compared with normal tissues [5]. EGFR signaling can induce epithelial to mesenchymal transition, invasion, and metastasis in different cancer cell types, including human breast cancer cells [7]
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