This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Cui, W. Articles by Akhurst, R. J. Search for Related Content PubMed PubMed Citation Articles by Cui, W. Articles by Akhurst, R. J.

Lack of Transforming Growth Factor-ß₁ Expression in Benign Skin Tumors of p53^null Mice Is Prognostic for a High Risk of Malignant Conversion¹

Department of Medical Genetics, University of Glasgow, Duncan Guthrie Institute, Yorkhill, Glasgow, G3 8SJ [W. C., E. D., R. J. A.], and the CRC Departments of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Alexander Stone Building, Garscube Estate, Bearsden, Glasgow G61 1BD [C. J. K., A. B.], United Kingdom

Expression of transforming growth factor ß1 (TGFß₁) protein was examined in chemically induced benign skin tumors with genetically defined empirical risks for malignant conversion. Benign tumors induced in mice which have both alleles of the p53 gene deleted have a malignant conversion frequency of 50%, whereas similar tumors induced in wild-type and heterozygous p53 mice have conversion probabilities of 3 and 8%, respectively (Kemp et al., Cell, 74: 813–822, 1993). The TGFß₁ antibody, anti-CC (1-30-1), was shown to stain either the proliferative keratinocyte compartment of the tumor or the tumor stroma, whereas another TGFß₁ antibody, anti-LC (1-30-1), stained highly differentiated granular cells of the tumors. A strong correlation was found between staining of the proliferative keratinocyte compartment of tumors with the anti-CC (1-30-1) antibody and tumor genotype. Only 18% (6 of 32) of homozygous p53 null tumors showed any basal keratinocyte staining with this antibody, whereas over 80% (32 of 38) of heterozygous and wild-type tumors showed positive staining. Additionally, in most tumors examined, the spatial distribution of staining for the proliferating cell nuclear antigen appeared to be mutually exclusive with that of TGFß₁ on adjacent serial sections. This suggests that, in these cases, tumor keratinocytes are sensitive to negative growth regulation by TGFß. TGFß₁ protein staining in benign tumors is thus prognostic for a low probability of malignant conversion, and its expression may be mechanistically involved in limiting malignant conversion since, at the benign tumor stage examined, keratinocytes are still sensitive to growth inhibition by TGFß₁.

¹ This work was supported by the Cancer Research Campaign.

² To whom requests for reprints should be addressed.

Received 3/30/94. Accepted 9/14/94.

This article has been cited by other articles:

				A. B. Glick, R. Perez-Lorenzo, and J. Mohammed Context-dependent regulation of cutaneous immunological responses by TGF{beta}1 and its role in skin carcinogenesis Carcinogenesis, January 1, 2008; 29(1): 9 - 14. [Abstract] [Full Text] [PDF]

				L. Yang, C. Mao, Y. Teng, W. Li, J. Zhang, X. Cheng, X. Li, X. Han, Z. Xia, H. Deng, et al. Targeted Disruption of Smad4 in Mouse Epidermis Results in Failure of Hair Follicle Cycling and Formation of Skin Tumors Cancer Res., October 1, 2005; 65(19): 8671 - 8678. [Abstract] [Full Text] [PDF]

				S.S. Prime, M. Davies, M. Pring, and I.C. Paterson THE ROLE OF TGF-{beta} IN EPITHELIAL MALIGNANCY AND ITS RELEVANCE TO THE PATHOGENESIS OF ORAL CANCER (PART II) Critical Reviews in Oral Biology & Medicine, November 1, 2004; 15(6): 337 - 347. [Abstract] [Full Text] [PDF]

				X. Liu, J. Lee, M. Cooley, E. Bhogte, S. Hartley, and A. Glick Smad7 but not Smad6 Cooperates with Oncogenic ras to Cause Malignant Conversion in a Mouse Model for Squamous Cell Carcinoma Cancer Res., November 15, 2003; 63(22): 7760 - 7768. [Abstract] [Full Text] [PDF]

				J. Laitakari and F. Stenback Collagen Matrix in Development and Progression of Experimentally Induced Respiratory Neoplasms in the Hamster Toxicol Pathol, August 1, 2001; 29(5): 514 - 527. [Abstract] [PDF]

				A. Glick, N. Popescu, V. Alexander, H. Ueno, E. Bottinger, and S. H. Yuspa Defects in transforming growth factor-beta signaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes PNAS, December 21, 1999; 96(26): 14949 - 14954. [Abstract] [Full Text] [PDF]

				P. C Rumsby Vital factors in liver cancer: M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity De Souza AT, Hankins GR, Washington MK, Orton TC and Jirtle RL. Nature Genetics 1995; 11: 447-449 Human and Experimental Toxicology, June 1, 1996; 15(6): 539 - 540. [Abstract] [PDF]

				W Cui, D J Fowlis, F M Cousins, E Duffie, S Bryson, A Balmain, and R J Akhurst Concerted action of TGF-beta 1 and its type II receptor in control of epidermal homeostasis in transgenic mice. Genes & Dev., April 15, 1995; 9(8): 945 - 955. [Abstract] [PDF]

				H. Yamada, K. Vijayachandra, C. Penner, and A. Glick Increased Sensitivity of Transforming Growth Factor (TGF) beta 1 Null Cells to Alkylating Agents Reveals a Novel Link between TGFbeta Signaling and O6-Methylguanine Methyltransferase Promoter Hypermethylation J. Biol. Chem., May 25, 2001; 276(22): 19052 - 19058. [Abstract] [Full Text] [PDF]