Insulin‐like growth factor II in two human colon‐carcinoma cell lines: Gene structure and expression, and protein secretion

Abstract

Abnormal expression and structural modification of the IGF-II gene in correlation with high IGF-II production have recently been described in human colorectal tumors in comparison with normal adjacent tissues. Here, we have studied IGF-II in 2 human colon-carcinoma cell lines, HT29 and COLO 320DM. RFLP analyses revealed no apparent alteration at the IGF-II locus in these 2 cell lines. HT29 cells weakly expressed IGF-II mRNA in comparison with the high over-expression previously observed in some colorectal tumors, and only the 4.8-kb mRNA species was present. In addition, the serum-free medium conditioned by HT29 cells contained high IGF-II levels (approx. 900 ng/10(8) cells), as measured in a specific IGF-II radioimmunoassay (RIA). After chromatography on Bio-Gel P-60, we observed that 64% of the total IGF-II secreted by HT29 cells were present as a high-molecular-weight form of about 17 kDa. In contrast, no detectable expression of the IGF-II gene was observed in COLO 320DM cells, and low IGF-II levels were secreted by these cells in the serum-free medium, with only 9% total IGF-II represented by the large species.

Expression of Insulin-Like Growth Factor-2 Can Predict the Prognosis of Human Colorectal Cancer Patients: Correlation with Tumor Progression, Proliferative Activity and Survival

“…After birth, IGF-2 levels decrease, and only a few tissues, for example liver and nerve, express IGF-2 in the adult [1][2][3][4]. Overexpression of IGF-2, however, has been reported in many types of tumors, including breast cancer, hepatoma, smooth muscle tumors, liposarcoma and others [5][6][7][8].…”

Decreased production of insulin‐like growth factor‐binding protein (IGFBP)‐6 by transfection of colon cancer cells with an antisense IGFBP‐6 cDNA construct leads to stimulation of cell proliferation

“…This is true of many colon carcinoma cell lines, including Caco‐2, 16,17 HT‐29, 25 SW613‐S, 26 COLO 205, 27 and several others 27 . Insulin‐like growth factor‐II mRNA is overexpressed in human colon carcinoma, compared with normal adjacent tissues 10 . Furthermore, ROI of IGF2 was found in an analysis of tumor tissue taken from 13 informative colorectal cancer patients 28 .…”

“…Several elements of the IGF axis exhibit altered expression in colon cancer and thereby may play a role in the development of this disorder. In human colon carcinoma, IGF‐II mRNA 10 and IGFBP‐2 mRNA 11 were overexpressed compared with normal adjacent tissues, and circulating IGF‐II and IGFBP‐2 were elevated 12 . Colon tumor tissues and tumor cell lines have a higher IGF‐I receptor number compared to normal mucosa 13 .…”

Combination of Anti-EGFR Drugs with Anti-Angiogenic or Other Signal Transduction Inhibitors as a Rational Approach to Cancer Therapy

“…In a human glioblastoma cell model, IGF-1R mediated resistance to anti-EGFR therapy partly through PI3K/AKT, providing a particularly clear example of redundancy of downstream signaling [23]. IGF2 mRNA and protein levels are overexpressed in approximately one third of colon cancers [24]. IGF-1R protein is expressed in over 90% of colon cancers, with almost no expression in corresponding normal mucosa.…”