Discordant transforming growth factor beta 1 RNA and protein localization during chemical carcinogenesis of the skin - PubMed (original) (raw)

Affiliations

PMID: 1504019

Discordant transforming growth factor beta 1 RNA and protein localization during chemical carcinogenesis of the skin

D J Fowlis et al. Cell Growth Differ. 1992 Feb.

Abstract

Transforming growth factor beta (TGF-beta) inhibits proliferation of normal keratinocytes, and this response is retained, to variable extents, in benign tumors of the skin (S. Haddow, D. J. Fowlis, K. Parkinson, R. J. Akhurst, and A. Balmain, Oncogene, 6: 1465-1470, 1991). To investigate the profile of TGF-beta biosynthesis during various stages of chemical carcinogenesis of the skin, we used a combination of ribonuclease protection assay, in situ hybridization with gene-specific probes for TGF-beta 1, -beta 2, and -beta 3, and immunohistochemistry with isoform-specific antibodies against TGF-beta 1. Following 12-O-tetradecanoylphorbol-13-acetate treatment of adult mouse skin, there was a rapid induction of TGF-beta 1 protein. Intracellular TGF-beta 1 protein was localized to suprabasal keratinocytes, and the extracellular form was localized predominantly to the dermis. Despite ubiquitous induction of TGF-beta 1 protein by 12-O-tetradecanoylphorbol-13-acetate in various mouse strains, we noted strain-specific differences in the quantitative induction of TGF-beta 1 RNA. Papillomas and carcinomas induced in vivo had elevated levels of TGF-beta 1 RNA within the basal keratinocyte compartment but did not contain significant levels of TGF-beta 1 protein within the tumor. We postulate that the tumor evades TGF-beta 1-controlled negative growth regulation by altered translational and/or posttranslational processing mechanisms of this growth factor. Levels of TGF-beta 2 and -beta 3 RNA were not elevated at any stage of chemical carcinogenesis of the skin.

PubMed Disclaimer

Cited by

Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.
Nakamura M, Katano M, Kuwahara A, Fujimoto K, Miyazaki K, Morisaki T, Mori M. Nakamura M, et al. Br J Cancer. 1998 Nov;78(10):1373-8. doi: 10.1038/bjc.1998.687. Br J Cancer. 1998. PMID: 9823982 Free PMC article.
Transgenic mice and squamous multistage skin carcinogenesis.
Brown K, Balmain A. Brown K, et al. Cancer Metastasis Rev. 1995 Jun;14(2):113-24. doi: 10.1007/BF00665795. Cancer Metastasis Rev. 1995. PMID: 7554029 Review.
Genetic variants of Tgfb1 act as context-dependent modifiers of mouse skin tumor susceptibility.
Mao JH, Saunier EF, de Koning JP, McKinnon MM, Higgins MN, Nicklas K, Yang HT, Balmain A, Akhurst RJ. Mao JH, et al. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8125-30. doi: 10.1073/pnas.0602581103. Epub 2006 May 15. Proc Natl Acad Sci U S A. 2006. PMID: 16702541 Free PMC article.
A conserved stem loop motif in the 5'untranslated region regulates transforming growth factor-β(1) translation.
Jenkins RH, Bennagi R, Martin J, Phillips AO, Redman JE, Fraser DJ. Jenkins RH, et al. PLoS One. 2010 Aug 26;5(8):e12283. doi: 10.1371/journal.pone.0012283. PLoS One. 2010. PMID: 20865036 Free PMC article.
Molecular mechanisms of mouse skin tumor promotion.
Rundhaug JE, Fischer SM. Rundhaug JE, et al. Cancers (Basel). 2010;2(2):436-82. doi: 10.3390/cancers2020436. Cancers (Basel). 2010. PMID: 21297902 Free PMC article.

Discordant transforming growth factor beta 1 RNA and protein localization during chemical carcinogenesis of the skin - PubMed (original) (raw)