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.
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.
Jiang
Yixing
Y
Department of Gastrointestinal Medical Oncology, The University of Texas, MD, Anderson Cancer Center, Houston, Texas 77030, USA.
Wang
Liwei
L
Gong
Weida
W
Wei
Daoyan
D
Le
Xiangdong
X
Yao
James
J
Ajani
Jaffer
J
Abbruzzese
James L
JL
Huang
Suyun
S
Xie
Keping
K
D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D017526:Receptor, IGF Type 1