Immunohistochemical localization of ornithine decarboxylase in skin tumors

Kagoura, Masayori; Toyoda, Masahiko; Matsui, Chieko; Morohashi, Masaaki

doi:10.1034/j.1600-0560.2000.027007338.x

Cited by 12 publications

(13 citation statements)

References 16 publications

(25 reference statements)

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“…Enhanced epidermal cyst formation has also been observed in the skin of some NBCCS patients (52,53). While ODC expression has not been assessed in the multiple BCCs in NBCCS patients (27), it seems highly likely that these lesions will manifest increased expression of this enzyme. A corollary to this hypothesis is that the epithelial lining of odontogenic keratinocysts in NBCCS patients has enhanced growth potential demonstrated by high expression of known proliferation markers such as PCNA and Ki67 (53)(54)(55)(56)(57)(58).…”

Section: Discussionmentioning

confidence: 98%

“…UVB rapidly induces papillomas and SCCs in transgenic mice with keratin 5 promoter-driven overexpression of ODC compared with non-transgenic littermates (25). It is unclear whether these mechanisms of tumor promotion that are pertinent to induction of SCCs are relevant to BCCs, although, as mentioned earlier, ODC activity is increased in BCCs (20,26,27). Cellular polyamine content is tightly regulated by various mechanisms, including transcriptional, translational, and posttranslational regulation of the enzymes responsible for polyamine synthesis and catabolism as well as a highly inducible polyamine-transport system (18,28).…”

Section: Introductionmentioning

confidence: 85%

“…The methods of scoring of carcinoma incidence and multiplicity, H&E staining, immunohistochemical analysis of Gli1, Ptch, hip, cyclin D1, and PCNA proteins, tissue lysate preparation, Western blotting, and measurement of ODC activity and polyamine levels were the same as published previously (16,20,21,27,31,32).…”

Section: Methodsmentioning

confidence: 99%

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Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/– mice

et al. 2004

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Solar ultraviolet B (UVB) radiation induces cutaneous ornithine decarboxylase (ODC), the first enzyme in the polyamine-biosynthesis pathway, which drives continued proliferation and clonal expansion of initiated (mutated) cells, leading to tumorigenesis. Therefore ODC is a potentially important target for chemoprevention of basal cell carcinomas (BCCs), the majority of which have mutations in the tumor-suppressor gene known as patched (PTCH). To assess this possibility, we first overexpressed ODC in the skin of Ptch1 +/-mice using a keratin 6 (K6) promoter that directs constitutive ODC expression in the outer root sheath of the hair follicle. UVB irradiation of these mice accelerated induction of BCCs as compared with their Ptch1 +/-littermates. To further verify the role of ODC in BCC tumorigenesis, we used an antizyme (AZ) approach to inhibit ODC activity in the Ptch1 +/-mice. Ptch1 +/-mice with AZ overexpression driven by the K6 promoter were resistant to the induction of BCCs by UVB. Furthermore, oral administration of the suicidal ODC inhibitor α α-difluoromethylornithine reduced UVB-induced BCCs in Ptch1 +/-mice. These results demonstrate the crucial importance of ODC for the induction of BCCs and indicate that chemopreventive strategies directed at inhibiting this enzyme may be useful in reducing BCCs in human populations.Nonstandard abbreviations used: basal cell carcinoma (BCC); α-difluoromethylornithine (DFMO); keratin 5 (K5); nevoid basal cell carcinoma syndrome (NBCCS); ornithine decarboxylase (ODC); antizyme (AZ); outer root sheath (ORS); patched (Ptch); sonic hedgehog (SHH); squamous cell carcinoma (SCC); ultraviolet B (UVB).

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 85%

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Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/– mice

et al. 2004

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“…O'Brien et al (39) showed that in transgenic mice, overexpression of ODC in skin was associated with elevated tissue polyamines, particularly putrescine and the development and maintenance of the neoplastic phenotype (40). ODC has also been found to be elevated in SCC compared with normal skin (41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Reproducibility and Expression of Skin Biomarkers in Sun-Damaged Skin and Actinic Keratoses

Einspahr

Warneke³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objectives: To explore p53 and proliferating cell nuclear antigen (PCNA) expression and polyamine content as biomarkers in skin cancer chemoprevention trials, we evaluated their expression in early stages of UV-induced squamous cell tumorigenesis. Methods: Biopsies were collected from three groups: 78 subjects with sun damage on forearms, 33 with actinic keratosis (AK) on forearms, and 32 with previous squamous cell carcinoma. Participants with sun damage were randomized to sunscreen or no sunscreen. Results: We found significant differences in p53 and polyamines in forearms from the sun-damaged group (11.5 F 1.2% for p53, 65.5 F 1.9 nmol/g for putrescine, and 187.7 F 3.3 nmol/g for spermidine) compared with the group with sun damage plus AK (20.9 F 2.3% for p53, P = 0.0001; 81.7 F 3.9 nmol/g for putrescine, P = 0.0001; 209.4 F 8.2 nmol/g for spermidine, P < 0.06). PCNA was not different. When lesion histology was considered, there was a stepwise significant increase in p53 in biopsies without characteristics of AK compared with early AK (P = 0.02) and AK (P = 0.0006) and a similar pattern for PCNA with the only significant difference between early AK and AK. There was a stepwise increase in putrescine and spermidine in normal, sun-damaged forearm, forearm from subjects with AK, and the AK lesion itself (P < 0.0001). No significant differences in p53 or polyamines were seen in 3-month biopsies or, as a result of sunscreen use, although PCNA in the sun-damaged group not using sunscreen decreased significantly. Conclusions: p53 expression and polyamines in skin were elevated in early stages of skin tumorigenesis and were not affected by sunscreen, adding validity to their use as biomarkers in skin cancer chemoprevention trials. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1841 -8)

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“…The skin specimens from acne patients, from control subjects and from organ culture were fixed in periodate‐lysine‐2% paraformaldehyde solution for 6 h at 4°C, rinsed in 0.01 M phosphate buffered saline (PBS) (pH 7.6) containing a series of graded concentrations of sucrose, and then embedded in OCT compound (Miles Scientific, Elkhart, IN, USA). Eight μm sections were cut using a cryostat, mounted on poly‐L‐lysine coated glass slides, and air dried at room temperature for 3 h. Immunohistochemistry was performed on these sections using an enhanced labeled polymer system conjugated to anti‐mouse and anti‐rabbit immunoglobulins (Dako, Kyoto, Japan), as previously described (20). After the specimens were rinsed with PBS, they were treated with 0.3% hydrogen peroxide in methanol for 10 min to inactivate endogenous peroxidase.…”

Section: Methodsmentioning

confidence: 99%

Sebaceous glands in acne patients express high levels of neutral endopeptidase

Toyoda

Nakamura

Makino

et al. 2002

Experimental Dermatology

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Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. To examine the possible involvement of neurogenic factors in the etiology of acne, we used immunohistochemistry to compare the distribution of SP-containing nerve fibers around sebaceous glands and the expression of neutral endopeptidase in sebaceous acini of the facial skin of acne patients and of healthy subjects. More numerous substance P immunoreactive nerve fibers in close apposition to the sebaceous glands and an increase in expression of neutral endopeptidase in sebaceous acini were observed in acne patients compared with the controls. Immunoelectron microscopy revealed that the subcellular localization of neutral endopeptidase was restricted to the Golgi apparatus and the endoplasmic reticulum within sebaceous germinative cells. In addition, in vitro experiments using an organ culture system demonstrated that substance P induced expression of neutral endopeptidase in sebaceous glands in a dose dependent manner. This study reveals that substance P and its degrading enzymes are involved in the pathogenesis of acne, which in turn might partially explain the pathologic significance of neurogenic and psychogenic aspects in the disease process.

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Immunohistochemical localization of ornithine decarboxylase in skin tumors

Cited by 12 publications

References 16 publications

Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/– mice

Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/– mice

Reproducibility and Expression of Skin Biomarkers in Sun-Damaged Skin and Actinic Keratoses

Sebaceous glands in acne patients express high levels of neutral endopeptidase

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