This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Greenhalgh, D. A. Articles by Roop, D. R. Search for Related Content PubMed PubMed Citation Articles by Greenhalgh, D. A. Articles by Roop, D. R.

Cooperation between v-fos and v-ras^HA Induces Autonomous Papillomas in Transgenic Epidermis but not Malignant Conversion¹

Departments of Cell Biology and Dermatology, Baylor College of Medicine, Houston, Texas 77030

Transgenic mice have been previously established that express v-ras^Ha or v-fos exclusively in the epidermis by means of a targeting vector based on the human keratin 1 gene (HK1). Epidermal expression of v-ras^Ha (HK1.ras) or v-fos (HK1.fos) resulted in hyperplasia, hyperkeratosis, and later, in benign tumors. To assess the potential for oncogene cooperation in vivo mating experiments were performed. Resultant HK1.fos/ras mice exhibited an obvious increase in the severity of neonatal and juvenile preneoplastic phenotypes, together with the immediate onset of tumorigenesis as compared to single oncogene sibling controls. The HK1.fos/ras tumors grew aggressively and often compromised the animals by 10–12 weeks. However, tumors remained benign as determined by histotype and specific keratin markers. These data indicate that v-fos can cooperate with an initiating v-ras^Ha phenotype to generate autonomous papillomas, but additional events are required for malignant conversion.

¹ This work was supported in part by NIH Grant CA52607 and a grant from the Texas Advanced Technology program (ATP004949048).

² To whom requests for reprints should be addressed, at Departments of Cell Biology and Dermatology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.

Received 8/23/93. Accepted 9/20/93.

This article has been cited by other articles:

				D. Yao, C. L. Alexander, J. A. Quinn, W.-C. Chan, H. Wu, and D. A. Greenhalgh Fos cooperation with PTEN loss elicits keratoacanthoma not carcinoma, owing to p53/p21WAF-induced differentiation triggered by GSK3{beta} inactivation and reduced AKT activity J. Cell Sci., May 15, 2008; 121(10): 1758 - 1769. [Abstract] [Full Text] [PDF]

				D. Yao, C. L. Alexander, J. A. Quinn, M. J. Porter, H. Wu, and D. A. Greenhalgh PTEN Loss Promotes rasHa-Mediated Papillomatogenesis via Dual Up-Regulation of AKT Activity and Cell Cycle Deregulation but Malignant Conversion Proceeds via PTEN-Associated Pathways Cancer Res., February 1, 2006; 66(3): 1302 - 1312. [Abstract] [Full Text] [PDF]

				K. L. Thompson and F. D. Sistare Selection of Drugs to Test the Specificity of the Tg.AC Assay by Screening for Induction of the gadd153 Promoter in Vitro Toxicol. Sci., August 1, 2003; 74(2): 260 - 270. [Abstract] [Full Text] [PDF]

				M. M. Mueller, W. Peter, M. Mappes, A. Huelsen, H. Steinbauer, P. Boukamp, M. Vaccariello, J. Garlick, and N. E. Fusenig Tumor Progression of Skin Carcinoma Cells in Vivo Promoted by Clonal Selection, Mutagenesis, and Autocrine Growth Regulation by Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Am. J. Pathol., October 1, 2001; 159(4): 1567 - 1579. [Abstract] [Full Text]

				X.-J. Wang, K. M. Liefer, S. Tsai, B. W. O'Malley, and D. R. Roop Development of gene-switch transgenic mice that inducibly express transforming growth factor beta 1 in the epidermis PNAS, July 20, 1999; 96(15): 8483 - 8488. [Abstract] [Full Text] [PDF]