Ornithine decarboxylase expression in cutaneous papillomas in SENCAR mice is associated with altered expression of keratins 1 and 10.
The patterns of expression of ornithine decarboxylase (ODC) and a number of keratinocyte differentiation products were examined in early papillomas by immunocytochemistry as an initial effort to develop phenotypic markers of the early stages of mouse skin tumorigenesis. Tumors were induced in SENCAR mice by initiation with 7,12-dimethylbenzanthracene, followed by once or twice weekly promotion treatments with 12-O-tetradecanoylphorbol-13-acetate. The patterns of immunocytochemical staining observed in early papillomas, collected after 7 weeks of promotion, were compared to those obtained with control skin and large, hyperkeratotic papillomas, collected after 23 weeks of promotion. In groups receiving 12-O-tetradecanoylphorbol-13-acetate, constitutive and induced ODC expression were evaluated either several days or 4.5 h after the last treatment, respectively. The major differentiation products in suprabasal keratinocytes are keratins, K1 and K10. These keratins were normally expressed in mildly hyperplastic epidermis, but staining became patchy in markedly hyperplastic epidermis. In early papillomas, K1 staining was patchy, and K10 staining occurred in very limited focal areas or was negative, such that the absence of staining delineated the lesions. Antibodies to the basal cell keratins, K5 and K14, stained both basal and suprabasal cells in hyperplastic epidermis and papillomas. Similarly, an antibody to keratin K6, which is expressed under conditions of hyperproliferation, uniformly stained the basal and suprabasal layers of hyperplastic epidermis and papillomas, demonstrating that the staining patterns observed with the antibodies to K1 and K10 were specific. Expression of ODC in the histologically normal skin of control mice was detected only in the hair follicles and depended on the hair cycle. Staining for induced ODC in mice treated with 12-O-tetradecanoylphorbol-13-acetate once weekly for 7 weeks was intense and diffuse throughout the suprabasal layers of the epidermis. In early and large papillomas, staining for constitutively expressed ODC was intense and diffuse in suprabasal cells. This intense staining for ODC occurred consistently in areas with decreased K1 and K10 expression, and, therefore, was associated with an altered pattern of differentiation. High constitutive ODC expression and decreased K1 and K10 expression will be useful phenotypic markers for studying the early stages of tumorigenesis in mouse skin.
Sundberg
J P
JP
Jackson Laboratory, Bar Harbor, Maine 04609.
Erickson
A A
AA
Roop
D R
DR
Binder
R L
RL
D015127:9,10-Dimethyl-1,2-benzanthracene; D000096:Acetone; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D000091344:Filaggrin Proteins; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000502:physiology; D007633:Keratins / Q000032:analysis / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D010212:Papilloma / Q000737:chemistry / Q000201:enzymology / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000503:physiopathology*
D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; C064554:loricrin; D000096:Acetone; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins; D009955:Ornithine Decarboxylase