EXPRESSION OF Hras-p21 AND KERATIN K13 IN UVR-INDUCED SKIN TUMORS IN SENCAR MICE

• Published in: Journal of Toxicology and Environmental Health, Part A Vol. 53; no. 6; pp. 439 - 453
• Main Authors: Tong, Y, Tucker, S B, Smith, M A
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 27.03.1998
• Subjects: Animals; Female; Keratins - metabolism; Mice; Mice, Inbred SENCAR; Mutation; Neoplasms, Radiation-Induced - metabolism; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; Skin Neoplasms - etiology; Skin Neoplasms - metabolism; Ultraviolet Rays - adverse effects
• ISSN: 1528-7394; 1087-2620
• DOI: 10.1080/009841098159178

An ultraviolet radiation (UVR)-induced Sencar mouse skin carcinogenesis model was established to investigate the expression of Hras-p21 and keratin K13 in different stages of carcinogenesis, including UV-exposed nontumor skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs) . Expression of Hras-p21 and K13 was examined in paraffin-embedded tumor sections by using immunohistochemical, immunofluorescent, and double staining techniques with specific antibodies. Positive Hras-p21 staining was detected in 1/ 3 (33%) papillomas, 24/ 36 (67%) of SCCs, but not in UVR-exposed nontumor skin or SCTs. Positive staining of the malignant progression marker K13 was found in 22/36 (61%) of SCCs only. Coexpression of Hrasp21 and K13 was found in 17/ 36 (47%) SCCs. H-ras exons 1 and 2 were amplified from skin/ tumor sections by using nested polymerase chain reaction (PCR). PCR-based single-strand conformation polymorphism (SSCP) analysis and gene sequencing revealed three point mutations, one in UVR-exposed nontumor skin (codon 56) , and two in SCCs (codons 13 and 21). There were no clear relationships between point mutations of H-ras and the positive staining of Hras-p21 and K13. These results indicate that overexpression of ras-p21 in conjunction with aberrant expression of K13 is a frequent event in UVR-induced SCCs in Sencar mouse skin. Point mutation of the H-ras gene appeared to be a rare event in UVR skin carcinogenesis and not to be responsible for overexpression of Hras-p21.