Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer.
Insulin-like growth factor I (IGF-I) activity has been reported to be produced by several human cancers. Identification of RNAs transcribed from the IGF-I gene has been complicated by the detection of multiple hybridizing bands on Northern analysis. To determine if any of these RNAs are transcribed from the IGF-I gene, we have used a sensitive and specific ribonuclease (RNAse) protection assay for IGF-I. We have also studied the breast cancer tissue expression of IGF-I using in situ hybridization histochemistry. We have found no IGF-I mRNA in breast (zero of 11) or colon cancer (zero of 9) cell lines; both of these tumors have been previously reported to express IGF-I mRNA. However, three of three neuroepithelioma and one of two Ewing's sarcoma cell lines express IGF-I mRNA; therefore, in these tumors IGF-I may be an autocrine growth factor. In contrast to breast cancer cell lines, RNA extracted from breast tissues has easily detectable IGF-I mRNA. In situ hybridizations show that IGF-I mRNA is expressed in the stromal cells, and not by normal or malignant epithelial cells. These findings suggest that although IGF-I is not produced by breast epithelial cells it may function as either a paracrine stimulator of epithelial cells or an autocrine stimulator of stromal cells.
Yee
D
D
Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.
Paik
S
S
Lebovic
G S
GS
Marcus
R R
RR
Favoni
R E
RE
Cullen
K J
KJ
Lippman
M E
ME
Rosen
N
N
D015152:Blotting, Northern; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D006729:Hormones, Ectopic / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D013002:Somatomedins / Q000235:genetics*; D014407:Tumor Cells, Cultured
D006729:Hormones, Ectopic; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I