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Altered expression of the epidermal growth factor receptor and transforming growth factor‐α during multistage skin carcinogenesis in SENCAR mice
Author(s) -
Rho Okkyung,
Beltrán Linda M.,
GimenezConti Irma B.,
Digiovanni John
Publication year - 1994
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/mc.2940110105
Subject(s) - carcinogenesis , biology , epidermal growth factor receptor , epidermis (zoology) , tumor promotion , tgf alpha , immunohistochemistry , transforming growth factor , cancer research , tumor initiation , messenger rna , epidermal growth factor , endocrinology , medicine , receptor , pathology , cancer , gene , immunology , anatomy , genetics
In the study presented here, we examined the possible role of the transforming growth factor‐α (TGFα)/epidermal growth factor receptor (EGFR) system during multistage carcinogenesis in mouse skin. In this regard, the expression (mRNA and protein) of both TGFα and EGFR was examined in primary papillomas and squamous cell carcinomas (SCCs) obtained from SENCAR mice treated with standard initiation‐promotion regimens and compared with the levels of expression in normal epidermis. The level of a 4.8‐kb TGFα transcript was elevated in 100% of the skin tumors examined (both papillomas and SCCs), including papillomas obtained 13 wk after the start of promotion, compared with normal epidermis. Immunohistochemical analyses detected elevated levels of TGFα protein in these skin tumors and in papillomas as early as 10 wk after the start of promotion. The levels of EGFR transcripts were also significantly elevated in most (90%) of the skin tumors examined, including again those harvested after 13 wk of promotion. Interestingly, multiple EGFR transcripts (10.5, 5.8, 2.8, and 1.8 kb) were detected in both papillomas and SCCs. The two smaller transcripts appeared to encode truncated versions of the EGFR , and the 1.8‐kb transcript appeared to be unique to RNA samples isolated from skin tumors, based on comparative analyses of several normal tissues. As with TGFα, immunohistochemical analyses detected elevated levels of EGFR protein in these skin tumors (both papillomas and SCCs), including papillomas harvested as early as 10 wk after the start of promotion. Southern analyses of genomic DNAs for TGFα and EGFR failed to detect any cases of gene rearrangements or amplification as a possible explanation for the elevated levels of the transcripts of these two genes. These results support the hypothesis that a key step in the development of autonomous growth in mouse skin papillomas generated in SENCAR mice by an initiation‐promotion regimen may involve alterations in the synthesis of TGFα and its cognate receptor. ©1994 Wiley‐Liss, Inc.