Abstract
A follicular origin for some skin tumors has been hypothesized in both humans and animal models. Because of its rapid and sensitive response to tumor promoter treatment, a v-Ha-ras transgenic (TG.AC) mouse line was used to determine the origins of epidermal papillomas. Using histological studies and transgene expression as a marker for papilloma development, we determined that pedunculated papillomas arose from focal hyperplasias of the permanent portion of the follicular epithelium in phorbol 12-myristate 13-acetate-treated TG.AC mouse skin. Damage to the hair follicle by depilation was also sufficient to induce papillomas that were histologically indistinguishable from those produced by chemical exposure. Identification of the cellular origins of papillomas in this transgenic mouse model will allow for an analysis of the role of the hair follicle and hair cycle-associated signaling in tumor development.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BILLINGHAM R. E., ORR J. W., WOODHOUSE D. L. Transplantation of skin components during chemical carcinogenesis with 20-methylcholanthrene. Br J Cancer. 1951 Dec;5(4):417–432. doi: 10.1038/bjc.1951.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bhisey R. A., Iyengar B., Sirsat S. M. Effect of the active tumor promoter, 12-O-tetradecanoylphorbol-13-acetate on hair follicular growth and development of hair anlage tumors in the mouse skin: a comparison with human adnexal lesions. J Cancer Res Clin Oncol. 1982;102(3):245–252. doi: 10.1007/BF00411344. [DOI] [PubMed] [Google Scholar]
- Chuong C. M., Chen H. M., Jiang T. X., Chia J. Adhesion molecules in skin development: morphogenesis of feather and hair. Ann N Y Acad Sci. 1991 Dec 26;642:263–280. doi: 10.1111/j.1749-6632.1991.tb24393.x. [DOI] [PubMed] [Google Scholar]
- Cotsarelis G., Sun T. T., Lavker R. M. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990 Jun 29;61(7):1329–1337. doi: 10.1016/0092-8674(90)90696-c. [DOI] [PubMed] [Google Scholar]
- GHADIALLY F. N. The role of the hair follicle in the origin and evolution of some cutaneous neoplasms of man and experimental animals. Cancer. 1961 Jul-Aug;14:801–816. doi: 10.1002/1097-0142(199007/08)14:4<801::aid-cncr2820140417>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
- Giovanella B. C., Liegel J., Heidelberger C. The refractoriness of the skin of hairless mice to chemical carcinogenesis. Cancer Res. 1970 Oct;30(10):2590–2597. [PubMed] [Google Scholar]
- Green M. R., Couchman J. R. Distribution of epidermal growth factor receptors in rat tissues during embryonic skin development, hair formation, and the adult hair growth cycle. J Invest Dermatol. 1984 Aug;83(2):118–123. doi: 10.1111/1523-1747.ep12263298. [DOI] [PubMed] [Google Scholar]
- Greenwell A., Foley J. F., Maronpot R. R. An enhancement method for immunohistochemical staining of proliferating cell nuclear antigen in archival rodent tissues. Cancer Lett. 1991 Sep;59(3):251–256. doi: 10.1016/0304-3835(91)90149-c. [DOI] [PubMed] [Google Scholar]
- Hansen L. A., Tennant R. Focal transgene expression associated with papilloma development in v-Ha-ras-transgenic TG.AC mice. Mol Carcinog. 1994 Mar;9(3):143–154. doi: 10.1002/mc.2940090306. [DOI] [PubMed] [Google Scholar]
- Hirai Y., Nose A., Kobayashi S., Takeichi M. Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis. Development. 1989 Feb;105(2):271–277. doi: 10.1242/dev.105.2.271. [DOI] [PubMed] [Google Scholar]
- Leder A., Kuo A., Cardiff R. D., Sinn E., Leder P. v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178–9182. doi: 10.1073/pnas.87.23.9178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller S. J., Sun T. T., Lavker R. M. Hair follicles, stem cells, and skin cancer. J Invest Dermatol. 1993 Mar;100(3):288S–294S. doi: 10.1111/1523-1747.ep12470169. [DOI] [PubMed] [Google Scholar]
- Miller S. J., Wei Z. G., Wilson C., Dzubow L., Sun T. T., Lavker R. M. Mouse skin is particularly susceptible to tumor initiation during early anagen of the hair cycle: possible involvement of hair follicle stem cells. J Invest Dermatol. 1993 Oct;101(4):591–594. doi: 10.1111/1523-1747.ep12366045. [DOI] [PubMed] [Google Scholar]
- Moore G. P., Panaretto B. A., Robertson D. Epidermal growth factor delays the development of the epidermis and hair follicles of mice during growth of the first coat. Anat Rec. 1983 Jan;205(1):47–55. doi: 10.1002/ar.1092050107. [DOI] [PubMed] [Google Scholar]
- Morris R. J., Fischer S. M., Slaga T. J. Evidence that the centrally and peripherally located cells in the murine epidermal proliferative unit are two distinct cell populations. J Invest Dermatol. 1985 Apr;84(4):277–281. doi: 10.1111/1523-1747.ep12265358. [DOI] [PubMed] [Google Scholar]
- Nanney L. B., Stoscheck C. M., King L. E., Jr, Underwood R. A., Holbrook K. A. Immunolocalization of epidermal growth factor receptors in normal developing human skin. J Invest Dermatol. 1990 Jun;94(6):742–748. doi: 10.1111/1523-1747.ep12874601. [DOI] [PubMed] [Google Scholar]
- Newbold R. R., Teng C. T., Beckman W. C., Jr, Jefferson W. N., Hanson R. B., Miller J. V., McLachlan J. A. Fluctuations of lactoferrin protein and messenger ribonucleic acid in the reproductive tract of the mouse during the estrous cycle. Biol Reprod. 1992 Nov;47(5):903–915. doi: 10.1095/biolreprod47.5.903. [DOI] [PubMed] [Google Scholar]
- Spalding J. W., Momma J., Elwell M. R., Tennant R. W. Chemically induced skin carcinogenesis in a transgenic mouse line (TG.AC) carrying a v-Ha-ras gene. Carcinogenesis. 1993 Jul;14(7):1335–1341. doi: 10.1093/carcin/14.7.1335. [DOI] [PubMed] [Google Scholar]
- Steinmuller D. A reinvestigation of epidermal transplantation during chemical carcinogenesis. Cancer Res. 1971 Dec;31(12):2080–2084. [PubMed] [Google Scholar]
- Tam J. P. Physiological effects of transforming growth factor in the newborn mouse. Science. 1985 Aug 16;229(4714):673–675. doi: 10.1126/science.3860952. [DOI] [PubMed] [Google Scholar]
- Weinberg W. C., Morgan D. L., George C., Yuspa S. H. A comparison of interfollicular and hair follicle derived cells as targets for the v-rasHa oncogene in mouse skin carcinogenesis. Carcinogenesis. 1991 Jun;12(6):1119–1124. doi: 10.1093/carcin/12.6.1119. [DOI] [PubMed] [Google Scholar]
- ZACKHEIM H. S. Origin of the human basal cell epithelioma. J Invest Dermatol. 1963 Jun;40:283–297. [PubMed] [Google Scholar]
- Zschiesche W., Eckert K. Effects of anti-EGF serum on newborn mice. Experientia. 1988 Mar 15;44(3):249–251. doi: 10.1007/BF01941725. [DOI] [PubMed] [Google Scholar]
- du Cros D. L., Isaacs K., Moore G. P. Localization of epidermal growth factor immunoreactivity in sheep skin during wool follicle development. J Invest Dermatol. 1992 Jan;98(1):109–115. doi: 10.1111/1523-1747.ep12496010. [DOI] [PubMed] [Google Scholar]