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Insulin-like growth factor I and transforming growth factor alpha as autocrine growth factors in human pancreatic cancer cell growth.
Cancer Res 1990; 50(1):103-7CR

Abstract

The roles of insulin-like growth factor I (IGF-I) and transforming growth factor alpha (TGF-alpha) as autocrine factors in the proliferation of MIA-PaCa 2 cells (human pancreatic cancer cells, PC cells) were investigated. Furthermore, the mechanism(s) of inhibition of PC cell growth by a phorbol ester in relation to these two kinds of growth factor was also studied. PC cells grew autonomously when Dulbecco's modified essential medium supplemented with 4% fetal calf serum was changed to serum-free medium (0.3% bovine serum albumin-Dulbecco's modified essential medium). In addition, serum-free conditioned medium from PC cells dialyzed against fresh Dulbecco's modified essential medium had a stimulatory action on the growth of the same kind of cells when compared with that induced by nonconditioned medium. These observations suggest that a factor(s) produced and released by PC cells stimulates their own growth. Analysis of conditioned medium from PC cells revealed the presence of immunoreactive (IR)-IGF-I and IR-TGF-alpha. The molecular size of IR-IGF-I was similar to that of authentic IGF-I. On the other hand, IR-TGF-alpha was present as multiple forms when analyzed using gel chromatography. Authentic IGF-I and TGF-alpha added to culture medium stimulated PC cell growth by 1.45- and 1.5-fold above control value, respectively. A monoclonal antibody to IGF-I receptor was able to inhibit PC cell growth. PC cell proliferation was markedly inhibited by 12-O-tetradecanoyl-13-acetate (greater than 0.16 nm), whereas cell growth of human fibroblasts was stimulated by it. 12-O-Tetradecanoyl-phorbol-13-acetate also reduced the binding of 125I-TGF-alpha, but not 125I-IGF-I, to PC cells. Decrease in TGF-alpha binding was mainly due to the reduced affinity of receptors to the ligand. These results suggest that IGF-I and TGF-alpha are involved in PC cell proliferation as autocrine factors. Further, the inhibition of PC cell growth by phorbol ester could be, at least partly, due to the decreased binding of TGF-alpha to the cells.

Authors+Show Affiliations

Department of Internal Medicine, Tokyo Women's Medical College, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2152769

Citation

Ohmura, E, et al. "Insulin-like Growth Factor I and Transforming Growth Factor Alpha as Autocrine Growth Factors in Human Pancreatic Cancer Cell Growth." Cancer Research, vol. 50, no. 1, 1990, pp. 103-7.
Ohmura E, Okada M, Onoda N, et al. Insulin-like growth factor I and transforming growth factor alpha as autocrine growth factors in human pancreatic cancer cell growth. Cancer Res. 1990;50(1):103-7.
Ohmura, E., Okada, M., Onoda, N., Kamiya, Y., Murakami, H., Tsushima, T., & Shizume, K. (1990). Insulin-like growth factor I and transforming growth factor alpha as autocrine growth factors in human pancreatic cancer cell growth. Cancer Research, 50(1), pp. 103-7.
Ohmura E, et al. Insulin-like Growth Factor I and Transforming Growth Factor Alpha as Autocrine Growth Factors in Human Pancreatic Cancer Cell Growth. Cancer Res. 1990 Jan 1;50(1):103-7. PubMed PMID: 2152769.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-like growth factor I and transforming growth factor alpha as autocrine growth factors in human pancreatic cancer cell growth. AU - Ohmura,E, AU - Okada,M, AU - Onoda,N, AU - Kamiya,Y, AU - Murakami,H, AU - Tsushima,T, AU - Shizume,K, PY - 1990/1/1/pubmed PY - 1990/1/1/medline PY - 1990/1/1/entrez SP - 103 EP - 7 JF - Cancer research JO - Cancer Res. VL - 50 IS - 1 N2 - The roles of insulin-like growth factor I (IGF-I) and transforming growth factor alpha (TGF-alpha) as autocrine factors in the proliferation of MIA-PaCa 2 cells (human pancreatic cancer cells, PC cells) were investigated. Furthermore, the mechanism(s) of inhibition of PC cell growth by a phorbol ester in relation to these two kinds of growth factor was also studied. PC cells grew autonomously when Dulbecco's modified essential medium supplemented with 4% fetal calf serum was changed to serum-free medium (0.3% bovine serum albumin-Dulbecco's modified essential medium). In addition, serum-free conditioned medium from PC cells dialyzed against fresh Dulbecco's modified essential medium had a stimulatory action on the growth of the same kind of cells when compared with that induced by nonconditioned medium. These observations suggest that a factor(s) produced and released by PC cells stimulates their own growth. Analysis of conditioned medium from PC cells revealed the presence of immunoreactive (IR)-IGF-I and IR-TGF-alpha. The molecular size of IR-IGF-I was similar to that of authentic IGF-I. On the other hand, IR-TGF-alpha was present as multiple forms when analyzed using gel chromatography. Authentic IGF-I and TGF-alpha added to culture medium stimulated PC cell growth by 1.45- and 1.5-fold above control value, respectively. A monoclonal antibody to IGF-I receptor was able to inhibit PC cell growth. PC cell proliferation was markedly inhibited by 12-O-tetradecanoyl-13-acetate (greater than 0.16 nm), whereas cell growth of human fibroblasts was stimulated by it. 12-O-Tetradecanoyl-phorbol-13-acetate also reduced the binding of 125I-TGF-alpha, but not 125I-IGF-I, to PC cells. Decrease in TGF-alpha binding was mainly due to the reduced affinity of receptors to the ligand. These results suggest that IGF-I and TGF-alpha are involved in PC cell proliferation as autocrine factors. Further, the inhibition of PC cell growth by phorbol ester could be, at least partly, due to the decreased binding of TGF-alpha to the cells. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/2152769/Insulin_like_growth_factor_I_and_transforming_growth_factor_alpha_as_autocrine_growth_factors_in_human_pancreatic_cancer_cell_growth_ L2 - http://www.diseaseinfosearch.org/result/5551 DB - PRIME DP - Unbound Medicine ER -