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

Clin Exp Metastasis. 2004;21(8):755-64. doi: 10.1007/s10585-005-1198-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Receptor, IGF Type 1 / metabolism*
  • Sp1 Transcription Factor / antagonists & inhibitors
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Survival Rate


  • RNA, Messenger
  • RNA, Small Interfering
  • Sp1 Transcription Factor
  • Receptor, IGF Type 1