A high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer

• DOI: 10.1007/s10585-005-1198-2
• Publication Date: 2005-05-27T12:05:55Z
• Authors: Yixing Jiang; Liwei Wang; Weida Gong; Daoyan Wei; Xiangdong Le; James Yao; Jaffer Ajani; James L. Abbruzzese; Suyun Huang; Keping Xie
• Keywords: Male; 0301 basic medicine; Sp1 Transcription Factor; Mice, Nude; Middle Aged; Prognosis; Receptor, IGF Type 1; 3. Good health; Gene Expression Regulation, Neoplastic; Survival Rate; Mice; 03 medical and health sciences; Stomach Neoplasms; Lymphatic Metastasis; Animals; Humans; Female; RNA, Messenger; RNA, Small Interfering

Insulin-like growth factor I receptor (IGF-IR) is critical to cell survival and growth and altered IGF-IR expression is found in many human cancers. However, its expression and potential role in gastric cancer development and progression has not been explored. The IGF-IR expression level was determined via immunohistochemistry in primary tumor and lymph node metastasis of 86 cases of resected gastric cancer. Relationships of IGF-IR expression with transcription factor Spl expression and clinicopathological features were analyzed. The impact of altered Sp1 expression on IGF-IR expression and gastric cancer biology was further determined using small inhibitory RNA for Sp1 mRNA. We found that IGF-IR was overexpressed in 62% of the tumor samples when compared with adjacent tumor-free gastric mucosa. Patients with lymph node metastases had strong expression of IGF-IR in both primary and metastatic tumor cells. IGF-IR overexpression in the primary tumor correlated with increased lymph node metastasis. Furthermore, the level of IGF-IR expression directly correlated with that of Spl, an important transcription factor for IGF-IR regulation. Knocking-down of Spl expression by small inhibitory RNA led to decreased IGF-IR expression and attenuated growth and metastasis of gastric cancer cells. Therefore, dysregulated expression of IGF-IR and/or Sp1 may contribute to the growth and metastasis of gastric cancer and potentially can be a target of therapeutic intervention.