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Clinical & Experimental Metastasis

, Volume 21, Issue 8, pp 755–764 | Cite as

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

  • Yixing Jiang
  • Liwei Wang
  • Weida Gong
  • Daoyan Wei
  • Xiangdong Le
  • James Yao
  • Jaffer Ajani
  • James L. Abbruzzese
  • Suyun Huang
  • Keping Xie
Article

Abstract

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 Sp1 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 Sp1, an important transcription factor for IGF-IR regulation. Knocking-down of Sp1 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.

Keywords

gastric cancer IGF-IR lymph node metastasis Sp1 transcription factor 

Abbreviations

AJCC

American Joint Committee on Cancer

CA

constitutive active

CI

confidence interval

DN

dominant-negative

IGF-IR

insulin-like growth factor receptor I

MVD

microvessel density

PBS

phosphate-buffered saline

siRNA

small inhibitory RNA

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Copyright information

© Springer 2005

Authors and Affiliations

  • Yixing Jiang
    • 1
  • Liwei Wang
    • 1
    • 4
  • Weida Gong
    • 2
  • Daoyan Wei
    • 1
  • Xiangdong Le
    • 1
  • James Yao
    • 1
  • Jaffer Ajani
    • 1
  • James L. Abbruzzese
    • 1
  • Suyun Huang
    • 2
  • Keping Xie
    • 1
    • 3
  1. 1.Department of Gastrointestinal Medical Oncology, Unit 426The University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Departments of NeurosurgeryThe University of TexasUSA
  3. 3.Departments of Cancer BiologyThe University of Texas, MD, Anderson Cancer Center, HoustonUSA
  4. 4.Shanghai East Hospital Cancer CenterTongji UniversityShanghaiThe People’s Republic of China

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