Actions of Insulin-Like Growth Factors

Froesch, E. R.; Schmid, C; Schwander, J; Zapf, J.

doi:10.1146/annurev.ph.47.030185.002303

Cited by 1,164 publications

(417 citation statements)

References 25 publications

Supporting

Mentioning

396

Contrasting

Unclassified

Order By: Relevance

“…IGF-II was of equal potency to insulin in the Eck's fistula model, although it also has little or no inherent mitogenicity in hepatocyte culture (42). IGF-II has been described in hepatomas in the woodchuck hepatitis model (43), and its role in modulating normal and neoplastic hepatocytes bears investigation.…”

Section: Discussionmentioning

confidence: 99%

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

Francavilla

1991

Hepatology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

Francavilla

1991

Hepatology

View full text Add to dashboard Cite

“…IGF-1 is expressed primarily in the liver, and circulates in an endocrinelike fashion with the assistance of binding proteins (Froesch et al, 1985;Shimasaki and Ling, 1991;Rechler and Brown, 1992). However, extrahepatic expression of the IGF-1 gene also occurs in a cell speci®c manner, where the action of the growth factor is paracrine.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice

et al. 1997

View full text Add to dashboard Cite

Transgenic animals were developed to assess the role of insulin-like growth factor 1 (IGF-1) in skin growth, di erentiation and organization, as well as its importance in tumor formation. Expression of a human IGF-1 cDNA was targeted to the interfollicular epidermis of transgenic mice using a human keratin 1 promoter construct (HK1). Transgenic animals (HK1.IGF-1 mice) could be identi®ed at birth by early ear unfolding and excessive ear and skin growth compared to nontransgenic littermates. Further examination of the skin from these mice showed epidermal hyperplasia and hyperkeratosis, marked thickening of the dermis and hypodermis, and early hair follicle generation in newborns. The severity of this phenotype correlated with transgene expression both of which subsided with age. Adult HK1.IGF-1 mice developed spontaneous tumors following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) alone and exhibited an exaggerated epidermal proliferative response following treatment with the tumor promoter compared to non transgenic littermates. Additionally, HK1.IGF-1 transgenic mice developed papillomas faster and in markedly greater numbers compared to non-transgenic littermates in standard initiation-promotion experiments. The data presented suggest an important role for IGF-1 in the process of multistage carcinogenesis in mouse skin.

show abstract

“…Synthesis of IGF-1 is induced primarily by GH but, in addition, growth factors like EGF and proto-oncogenes like c-myb may be involved (Pietrzkowski et al, 1993). IGF-I is synthesized and secreted mostly by the liver, but also by other tissues, such as lung and kidney (Froesch et al, 1985). Various cancer cells are likewise able to produce and secrete insulin-like growth factors (Macaulay, 1992), among them PC-3 and DU-145 prostate cancer cell lines (Pietrzkowski et al, 1993).…”

mentioning

confidence: 99%

Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone

Jungwirth

Schally²,

Pinski³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Tumour-inhibitory effects of a new antagonist of growth hormone-releasing hormone (GH-RH), MZ-4-71, were evaluated in nude mice bearing androgen-independent human prostate cancer cell lines DU-145 and PC-3 and in Copenhagen rats implanted with Dunning R-3327 AT-1 prostatic adenocarcinoma. After 6 weeks of therapy, the tumour volume in nude mice with DU-1 45 prostate cancers treated with 40 ,ug day-' MZ-4-71 was significantly decreased to 37 ± 13 mm3 (P < 0.01) compared with controls that measured 194 ± 35 mm3. A similar inhibition of tumour growth was obtained in nude mice bearing PC-3 cancers, in which the treatment with MZ-4-71 for 4 weeks diminished the tumour volume to 1 19 ± 35 mm3 compared with 397 ± 115 mm3 for control animals. Therapy with MZ-4-71 also significantly decreased weights of PC-3 and DU-145 tumours and increased tumour doubling time. Serum levels of GH and IGF-I were significantly decreased in animals treated with GH-RH antagonist. In PC-3 tumour tissue, the levels of IGF-I and IGF-II were reduced to non-detectable values after therapy with MZ-4-71. The growth of Dunning R-3327 AT-1 tumours in rats was also significantly inhibited after 3 weeks of treatment with 100 gg of MZ-4-71 day-' i.p. as shown by a reduction in tumour volume and weight (both P-values < 0.05). Specific high-affinity binding sites for IGF-I were found on the membranes of DU-145, PC-3 and Dunning R-3327 AT-1 tumours. Our results indicate that GH-RH antagonist MZ-4-71 suppresses growth of PC-3, DU-145 and Dunning AT-I androgen-independent prostate cancers, through diminution of GH release and the resulting decrease in the secretion of hepatic IGF-I, or through mechanisms involving a lowering of tumour IGF-I levels and possibly an inhibition of tumour IGF-I and IGF-Il production. GH-RH antagonists could be considered for further development for the therapy of prostate cancer, especially after the relapse.

show abstract

Actions of Insulin-Like Growth Factors

Cited by 1,164 publications

References 25 publications

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice

Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone

Contact Info

Product

Resources

About