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

Original Paper
Published: 10 April 1997

Oncogene volume 14, pages 1725–1734 (1997)Cite this article

990 Accesses
125 Citations
Metrics details

Abstract

Transgenic animals were developed to assess the role of insulin-like growth factor 1 (IGF-1) in skin growth, differentiation 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 identified at birth by early ear unfolding and excessive ear and skin growth compared to non-transgenic 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.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 50 print issues and online access

$259.00 per year

only $5.18 per issue

Buy this article

Purchase on SpringerLink
Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Author information

Authors and Affiliations

Department of Carcinogenesis, Research Division, The University of Texas MD, Anderson Cancer Center, Science Park, Smithville, 78957, Texas, USA
David K Bol, Kaoru Kiguchi, Irma Gimenez-Conti, Tim Rupp & John DiGiovanni

Authors

David K Bol
Kaoru Kiguchi
Irma Gimenez-Conti
Tim Rupp
John DiGiovanni

Rights and permissions

About this article

Cite this article

Bol, D., Kiguchi, K., Gimenez-Conti, I. et al. Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice.Oncogene 14, 1725–1734 (1997). https://doi.org/10.1038/sj.onc.1201011

Download citation

Received: 25 October 1996
Revised: 23 December 1996
Accepted: 06 January 1997
Issue date: 10 April 1997
DOI: https://doi.org/10.1038/sj.onc.1201011