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恶性肿瘤中胰岛素样生长因子I基因表达的分析:其在人类乳腺癌中旁分泌作用的证据

Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer.

作者信息

Yee D, Paik S, Lebovic G S, Marcus R R, Favoni R E, Cullen K J, Lippman M E, Rosen N

机构信息

Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.

出版信息

Mol Endocrinol. 1989 Mar;3(3):509-17. doi: 10.1210/mend-3-3-509.

DOI:10.1210/mend-3-3-509
PMID:2747657
Abstract

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.

摘要

胰岛素样生长因子I(IGF-I)活性已被报道可由多种人类癌症产生。由于在Northern分析中检测到多个杂交带,IGF-I基因转录的RNA的鉴定变得复杂。为了确定这些RNA中是否有任何一种是从IGF-I基因转录而来,我们使用了一种灵敏且特异的IGF-I核糖核酸酶(RNAse)保护试验。我们还使用原位杂交组织化学研究了乳腺癌组织中IGF-I的表达。我们在乳腺癌(11个样本中0个)或结肠癌细胞系(9个样本中0个)中未发现IGF-I mRNA;此前已有报道称这两种肿瘤均表达IGF-I mRNA。然而,三种神经上皮瘤细胞系中的三种以及两种尤因肉瘤细胞系中的一种表达IGF-I mRNA;因此,在这些肿瘤中IGF-I可能是一种自分泌生长因子。与乳腺癌细胞系不同,从乳腺组织提取的RNA中可轻松检测到IGF-I mRNA。原位杂交显示IGF-I mRNA在基质细胞中表达,而不在正常或恶性上皮细胞中表达。这些发现表明,尽管IGF-I不是由乳腺上皮细胞产生的,但它可能作为上皮细胞的旁分泌刺激因子或基质细胞的自分泌刺激因子发挥作用。

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