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Altered expression of insulin‐like growth factor I and its receptor during multistage carcinogenesis in mouse skin
Author(s) -
Rho Okkyung,
Bol David K.,
You Jinsong,
Beltrán Linda,
Rupp Tim,
DiGiovanni John
Publication year - 1996
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199610)17:2<62::aid-mc2>3.0.co;2-v
Subject(s) - biology , dermis , epidermis (zoology) , carcinogenesis , microbiology and biotechnology , insulin like growth factor 2 , messenger rna , epidermal growth factor receptor , northern blot , receptor , tumor promotion , reverse transcription polymerase chain reaction , endocrinology , gene expression , growth factor , medicine , gene , biochemistry , anatomy
Abstract We examined the possible role of insulin‐like growth factor‐I (IGF‐I) and IGF‐I receptor (IGF‐Ir) during multistage carcinogenesis in mouse skin. For this purpose, the expression of both IGF‐I and IGF‐Ir was investigated in mouse skin during tumor promoter treatment and in primary papillomas and squamous cell carcinomas (SCCs) obtained from SENCAR mice treated with standard initiation‐promotion regimens. IGF‐I transcripts were not detectable or only weakly detectable in normal SENCAR mouse epidermis by northern or reverse transcription (RT)‐polymerase chain reaction (PCR) analysis, respectively, whereas IGF‐I transcripts (primarily a 7.0‐kb transcript) were readily detected in RNA preparations from the dermis by both northern blot analysis and RT‐PCR analysis. In contrast, IGF‐Ir transcripts were observed in RNA samples from both epidermis and dermis of control SENCAR mice. Single and multiple topical treatments with 3.4 nmol of 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) had no effect on dermal or epidermal IGF‐I and IGF‐Ir mRNA levels. In contrast, the levels of IGF‐I transcripts were elevated (2.5‐ to 15‐fold) in a significant number of mouse skin tumors (71% of all tumors examined). Transcripts of 7.0, 2.5, and 1.3 kb were more consistently overexpressed in skin tumors compared with epidermis, whereas the two smaller transcripts were most consistently overexpressed compared with the dermis. The levels of an 11.0‐kb IGF‐Ir transcript were also elevated (2.5‐ to 8‐fold) in some papillomas (20%) and SCCs (55%), but the percentage of tumors exhibiting this property (32% of all tumors examined) was lower than the percentage overexpressing IGF‐I . These data suggest that altered expression of IGF‐I and IGF‐Ir may play a role in multistage carcinogenesis in the mouse skin model. The inability of TPA to induce elevated IGF‐I or IGF‐Ir expression suggests that these changes in skin tumors are coincident with tumor formation and not a direct result of altered epidermal proliferation per se. Altered expression of IGF‐I in a high percentage of papillomas may indicate that IGF‐I has an important role in the development of autonomous growth in these tumors. The higher percentage of SCCs with altered levels of IGF‐Ir mRNA may indicate a role for these changes in the later stages (i.e., tumor progression) of carcinogenesis in this model system. © 1996 Wiley‐Liss, Inc.