Expression level of insulin‐like growth factor binding protein 5 mRNA is a prognostic factor for breast cancer

Abstract

The role of insulin-like growth factor binding protein 5 (IGFBP5) in tumorigenesis and development of cancer is not well-defined. IGFBP5 has been shown to either stimulate or inhibit cell proliferation via an IGF-dependent mechanism and to promote cell proliferation and migration in an IGF-independent manner. In the authors' previous study, IGFBP5 was found to be significantly up-regulated in lymph node metastases compared with their paired primary breast cancers. To further determine the role of IGFBP5 in breast cancer development and to evaluate its clinical significance in breast cancer, the mRNA expression level was detected in 30 normal breast tissues, 108 primary tumors, and 30 lymph node metastases using real time reverse transcription-polymerase chain reaction. The expression levels were correlated with several clinical parameters, including clinical stage, pathologic tumor size, axillary lymph node status, nuclear grade, estrogen receptor status, Her2 status, and local relapse or distant metastasis of the patients. As a result, the expression of IGFBP5 mRNA correlated positively with the invasion of axillary lymph nodes and the status of hormonal receptor. T he insulin-like growth factor binding protein 5 (IGFBP5) belongs to a protein family of at least six members that binds to insulin-like growth factor (IGF). In humans, the IGFBP5 gene spans 33 kb and is located on 2q33-q36. The mature IGFBP5 protein consists of 252 amino acids and has a molecular mass of approximately 29 kDa. IGFBP5 was initially recognized as a secreted protein that binds to IGF with high affinity by its N-terminal motif and modulates their mitogenic and anti-apoptotic effects by either inhibiting or augmenting the interaction of IGF with their cell-surface receptor (IGF-IR). IGFBP5 has been shown to inhibit the proliferative responses of skeletal muscle cells (1) and breast cancer cells (2) to IGF-I. In contrast, in bone, (3) fibroblast, (4) osteoblasts, (5) and vascular smooth muscle cells, (6) IGFBP5 has been found to potentiate the effect of IGF on cell growth. The complexity of the cellular function of IGFBP and its regulation is further revealed by recent studies that have shown that IGFBP5 also stimulates cell growth, (7,8) migration, (6,9,10) and cell attachment to extracellular matrix (ECM) (11,12) through IGF-independent mechanisms. Thus, the role of IGFBP5 in cancer is far from being clear.In the authors' previous study of breast cancer tissues,it was found that IGFBP5 was significantly up-regulated in lymph node metastases relative to their paired primary cancers, suggesting that IGFBP5 may play an important role in the metastasis of breast cancer. Additional studies have supported the notion that IGFBP5 overexpression contributes to metastasis and poor prognosis of cancer. Wang et al. have demonstrated a strong correlation between overexpression of IGFBP5 and the histologic grade of ovarian cancer and glioblastoma. (14,15) And up-regulated IGFBP5 was included in the 'poor prognosis signature' in a study by van't Veer e...

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