Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes

doi:10.1083/jcb.98.4.1397

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Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes

RA Weiss, R Eichner and TT Sun

The polypeptide composition of epidermal keratin varies in disease. To better understand the biological meaning of these variations, we have analyzed keratins from a number of human epidermal diseases by the immunoblot technique using AE1 and AE3 monoclonal antikeratin antibodies. The results reveal a continuous spectrum of keratin expression ranging from one closely resembling the normal in vivo pattern to one almost identical to cultured epidermal keratinocytes. Specifically, a 50-kilodalton (kd) (AE1-positive) and a 58-kd (AE3- positive) keratin are present in all diseases, supporting the concept that they represent "permanent" markers for keratinocytes. A 56.5-kd (AE1) and a 65-67-kd (AE3) keratin, previously shown to be markers for keratinization, are expressed only by lesions retaining a keratinized morphology. A 48-kd (AE1) and a 56-kd (AE3) keratin are present in all hyperproliferative (para- or nonkeratinized) disorders, but not in normal abdominal epidermis or in ichthyosis vulgaris which is a nonhyperproliferative disease. These two keratins have previously been found in various nonepidermal keratinocytes undergoing hyperproliferation, suggesting that these keratins are not epidermis- specific and may represent markers for hyperproliferative keratinocytes in general. In various epidermal diseases, there is a reciprocal expression of the (keratin) markers for hyperproliferation and keratinization, supporting the mutual exclusiveness of the two cellular events. Moreover, our results indicate that, as far as keratin expression is concerned, cultured human epidermal cells resemble and thus may be regarded as a model for epidermal hyperplasia. Finally, the apparent lack of any major, disease-specific keratin changes in the epidermal disorders studied so far implies that keratin abnormalities probably represent the consequence, rather than the cause, of these diseases.
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Shin, J., Monti, S., Aires, D. J., Duvic, M., Golub, T., Jones, D. A., Kupper, T. S. (2007). Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome. Blood 110: 3015-3027 [Abstract] [Full Text]
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Leslie, M. (2005). Tagging an organelle. JCB 171: 195-195 [Full Text]
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Ruiz, S., Santos, M., Segrelles, C., Leis, H., Jorcano, J. L., Berns, A., Paramio, J. M., Vooijs, M. (2004). Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis. Development 131: 2737-2748 [Abstract] [Full Text]
List, K., Szabo, R., Wertz, P. W., Segre, J., Haudenschild, C. C., Kim, S.-Y., Bugge, T. H. (2003). Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1. JCB 163: 901-910 [Abstract] [Full Text]
Oike, Y., Yasunaga, K., Ito, Y., Matsumoto, S.-i., Maekawa, H., Morisada, T., Arai, F., Nakagata, N., Takeya, M., Masuho, Y., Suda, T. (2003). Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration. Proc. Natl. Acad. Sci. USA 100: 9494-9499 [Abstract] [Full Text]
Rea, M. A., Gregg, J. P., Qin, Q., Phillips, M. A., Rice, R. H. (2003). Global alteration of gene expression in human keratinocytes by inorganic arsenic. Carcinogenesis 24: 747-756 [Abstract] [Full Text]
Bloor, B. K., Tidman, N., Leigh, I. M., Odell, E., Dogan, B., Wollina, U., Ghali, L., Waseem, A. (2003). Expression of Keratin K2e in Cutaneous and Oral Lesions: Association with Keratinocyte Activation, Proliferation, and Keratinization. Am. J. Pathol. 162: 963-975 [Abstract] [Full Text]
Santos, M., Bravo, A., Lopez, C., Paramio, J. M., Jorcano, J. L. (2002). Severe Abnormalities in the Oral Mucosa Induced by Suprabasal Expression of Epidermal Keratin K10 in Transgenic Mice. J. Biol. Chem. 277: 35371-35377 [Abstract] [Full Text]
Santos, M., Paramio, J. M., Bravo, A., Ramirez, A., Jorcano, J. L. (2002). The Expression of Keratin K10 in the Basal Layer of the Epidermis Inhibits Cell Proliferation and Prevents Skin Tumorigenesis. J. Biol. Chem. 277: 19122-19130 [Abstract] [Full Text]
Miliani de Marval, P. L., Gimenez-Conti, I. B., LaCava, M., Martinez, L. A., Conti, C. J., Rodriguez-Puebla, M. L. (2001). Transgenic Expression of Cyclin-Dependent Kinase 4 Results in Epidermal Hyperplasia, Hypertrophy, and Severe Dermal Fibrosis. Am. J. Pathol. 159: 369-379 [Abstract] [Full Text]
Reichelt, J., Bussow, H., Grund, C., Magin, T. M. (2001). Formation of a Normal Epidermis Supported by Increased Stability of Keratins 5 and 14 in Keratin 10 Null Mice. Mol. Biol. Cell 12: 1557-1568 [Abstract] [Full Text]
Peters, B., Kirfel, J., Bussow, H., Vidal, M., Magin, T. M. (2001). Complete Cytolysis and Neonatal Lethality in Keratin 5 Knockout Mice Reveal Its Fundamental Role in Skin Integrity and in Epidermolysis Bullosa Simplex. Mol. Biol. Cell 12: 1775-1789 [Abstract] [Full Text]
Wertheimer, E., Spravchikov, N., Trebicz, M., Gartsbein, M., Accili, D., Avinoah, I., Nofeh-Moses, S., Sizyakov, G., Tennenbaum, T. (2001). The Regulation of Skin Proliferation and Differentiation in the IR Null Mouse: Implications for Skin Complications of Diabetes. Endocrinology 142: 1234-1241 [Abstract] [Full Text]
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Longan, L., Longnecker, R. (2000). Epstein-Barr virus latent membrane protein 2A has no growth-altering effects when expressed in differentiating epithelia. J. Gen. Virol. 81: 2245-2252 [Abstract] [Full Text]
Wakita, H., Takigawa, M. (1999). Activation of Epidermal Growth Factor Receptor Promotes Late Terminal Differentiation of Cell-Matrix Interaction-disrupted Keratinocytes. J. Biol. Chem. 274: 37285-37291 [Abstract] [Full Text]
Paladini, R. D., Coulombe, P. A. (1999). The Functional Diversity of Epidermal Keratins Revealed by the Partial Rescue of the Keratin 14 Null Phenotype by Keratin 16. JCB 146: 1185-1201 [Abstract] [Full Text]
Paramio, J. M., Casanova, M. L., Segrelles, C., Mittnacht, S., Lane, E. B., Jorcano, J. L. (1999). Modulation of Cell Proliferation by Cytokeratins K10 and K16. Mol. Cell. Biol. 19: 3086-3094 [Abstract] [Full Text]
Manabe, M., Lim, H. W., Winzer, M., Loomis, C. A. (1999). Architectural Organization of Filiform Papillae in Normal and Black Hairy Tongue Epithelium: Dissection of Differentiation Pathways in a Complex Human Epithelium According to Their Patterns of Keratin Expression. Arch Dermatol 135: 177-181 [Abstract] [Full Text]
Porter, R. M., Hutcheson, A. M., Rugg, E. L., Quinlan, R. A., Lane, E. B. (1998). cDNA Cloning, Expression, and Assembly Characteristics of Mouse Keratin 16. J. Biol. Chem. 273: 32265-32272 [Abstract] [Full Text]
Laplante, A. F., Moulin, V., Auger, F. A., Landry, J., Li, H., Morrow, G., Tanguay, R. M., Germain, L. (1998). Expression of Heat Shock Proteins in Mouse Skin During Wound Healing. J. Histochem. Cytochem. 46: 1291-1302 [Abstract] [Full Text]
McGowan, K. M., Coulombe, P. A. (1998). Onset of Keratin 17 Expression Coincides with the Definition of Major Epithelial Lineages during Skin Development. JCB 143: 469-486 [Abstract] [Full Text]
Paladini, R. D., Coulombe, P. A. (1998). Directed Expression of Keratin 16 to the Progenitor Basal Cells of Transgenic Mouse Skin Delays Skin Maturation. JCB 142: 1035-1051 [Abstract] [Full Text]
Wawersik, M., Paladini, R. D., Noensie, E., Coulombe, P. A. (1997). A Proline Residue in the alpha -Helical Rod Domain of Type I Keratin 16�Destabilizes Keratin Heterotetramers. J. Biol. Chem. 272: 32557-32565 [Abstract] [Full Text]
Takahashi, K., Coulombe, P. A. (1997). Defining a Region of the Human Keratin 6a Gene That Confers Inducible Expression in Stratified Epithelia of Transgenic Mice. J. Biol. Chem. 272: 11979-11985 [Abstract] [Full Text]
Wang, X.-J., Greenhalgh, D. A., Bickenbach, J. R., Jiang, A., Bundman, D. S., Krieg, T., Derynck, R., Roop, D. R. (1997). Expression of a dominant-negative type II transforming growth factor beta �(TGF-beta ) receptor in the epidermis of transgenic mice blocks TGF-beta -mediated growth�inhibition. Proc. Natl. Acad. Sci. USA 94: 2386-2391 [Abstract] [Full Text]
Reichelt, J, Bauer, C, Porter, R, Lane, E, Magin, V (1997). Out of balance: consequences of a partial keratin 10 knockout. J. Cell Sci. 110: 2175-2186 [Abstract]
Takahashi, K., Coulombe, P.�A. (1996). A transgenic mouse model with an inducible skin blistering disease�phenotype. Proc. Natl. Acad. Sci. USA 93: 14776-14781 [Abstract] [Full Text]
Tomic-Canic, M., Day, D., Samuels, H. H., Freedberg, I. M., Blumenberg, M. (1996). Novel Regulation of Keratin Gene Expression by Thyroid Hormone and Retinoid Receptors. J. Biol. Chem. 271: 1416-1423 [Abstract] [Full Text]
Navarro, J. M., Casatorres, J., Jorcano, J. L. (1995). Elements Controlling the Expression and Induction of the Skin Hyperproliferation-associated Keratin K6. J. Biol. Chem. 270: 21362-21367 [Abstract] [Full Text]
Takahashi, K., Paladini, R. D., Coulombe, P. A. (1995). Cloning and Characterization of Multiple Human Genes and cDNAs Encoding Highly Related Type II Keratin 6 Isoforms. J. Biol. Chem. 270: 18581-18592 [Abstract] [Full Text]
Imakado, S, Bickenbach, J R, Bundman, D S, Rothnagel, J A, Attar, P S, Wang, X J, Walczak, V R, Wisniewski, S, Pote, J, Gordon, J S (1995). Targeting expression of a dominant-negative retinoic acid receptor mutant in the epidermis of transgenic mice results in loss of barrier function.. Genes Dev. 9: 317-329 [Abstract]
Rugg, E L, McLean, W H, Lane, E B, Pitera, R, McMillan, J R, Dopping-Hepenstal, P J, Navsaria, H A, Leigh, I M, Eady, R A (1994). A functional "knockout" of human keratin 14.. Genes Dev. 8: 2563-2573 [Abstract]
Eicher, S. A., Taylor-Cooley, L. D., Donovan, D. T. (1994). Isotretinoin Therapy for Recurrent Respiratory Papillomatosis. Arch Otolaryngol Head Neck Surg 120: 405-409 [Abstract]
Alkemade, J., Molhuizen, H., Ponec, M, Kempenaar, J., Zeeuwen, P., de Jongh, G., van Vlijmen-Willems, I., van Erp, P., van de Kerkhof, P., Schalkwijk, J (1994). SKALP/elafin is an inducible proteinase inhibitor in human epidermal keratinocytes. J. Cell Sci. 107: 2335-2342 [Abstract]
Dale, B. A., Kam, E. (1993). Harlequin Ichthyosis: Variability in Expression and Hypothesis for Disease Mechanism. Arch Dermatol 129: 1471-1477 [Abstract]
Pang, Y., Schermer, A, Yu, J, Sun, T. (1993). Suprabasal change and subsequent formation of disulfide-stabilized homo- and hetero-dimers of keratins during esophageal epithelial differentiation. J. Cell Sci. 104: 727-740 [Abstract]
Vassar, R, Fuchs, E (1991). Transgenic mice provide new insights into the role of TGF-alpha during epidermal development and differentiation.. Genes Dev. 5: 714-727 [Abstract]
Steinberg, B. M., Meade, R., Kalinowski, S., Abramson, A. L. (1990). Abnormal Differentiation of Human Papillomavirus-Induced Laryngeal Papillomas. Arch Otolaryngol Head Neck Surg 116: 1167-1171 [Abstract]
Dale, B. A., Salonen, J., Jones, A. H. (1990). New Approaches And Concepts in The Study of Differentiation of Oral Epithelia. CROBM 1: 167-190 [Abstract] [Full Text]
Kopan, R, Fuchs, E (1989). A new look into an old problem: keratins as tools to investigate determination, morphogenesis, and differentiation in skin.. Genes Dev. 3: 1-15 [Abstract]
Moriwaki, S.-i., Tanaka, T., Horiguchi, Y., Danno, K., Imamura, S. (1988). Epidermolytic Hereditary Palmoplantar Keratoderma Histologic, Ultrastructural, Protein-Chemical, and DNA Analyses in Two Patients. Arch Dermatol 124: 555-559 [Abstract]
Komine, M., Rao, L. S., Kaneko, T., Tomic-Canic, M., Tamaki, K., Freedberg, I. M., Blumenberg, M. (2000). Inflammatory Versus Proliferative Processes in Epidermis. TUMOR NECROSIS FACTOR alpha INDUCES K6b KERATIN SYNTHESIS THROUGH A TRANSCRIPTIONAL COMPLEX CONTAINING NFkappa B AND C/EBPbeta. J. Biol. Chem. 275: 32077-32088 [Abstract] [Full Text]