Cyclooxygenase-1 Deletion Enhances Apoptosis but Does Not Protect Against Ultraviolet Light-Induced Tumors
| Autor: | Carol Tanck, JoAnne VanBuskirk, Gina N. LaRossa, Sabine M. Brouxhon, Glynis Scott, Alice P. Pentland |
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| Rok vydání: | 2004 |
| Předmět: |
Keratinocytes
Male Cancer Research Programmed cell death Skin Neoplasms Ultraviolet Rays medicine.medical_treatment Apoptosis Biology medicine.disease_cause Mice Ultraviolet light medicine Animals Skin Mice Hairless Cancer medicine.disease Molecular biology Hairless Isoenzymes Mice Inbred C57BL Oncology Terminal deoxynucleotidyl transferase Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Immunology Female Carcinogenesis Cell Division Prostaglandin E |
| Zdroj: | Cancer Research. 64:5587-5591 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-04-1045 |
| Popis: | Inhibition or deletion of cyclooxygenase (COX)-2 has been demonstrated to protect against squamous cell cancer in many studies. Although much effort has focused on COX-2 inhibition, recent work indicates that COX-1 deletion may be nearly as protective. In this study, we used SKH-1 hairless mice in which COX-1 was selectively deleted to examine the role of COX-1 in photocarcinogenesis. After UV exposure, 40–60% less prostaglandin E2 was detected in COX-1−/− animals compared with wild-type (WT) controls. A 4-fold induction of keratinocyte apoptosis was observed in knockouts relative to WT animals, as documented by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling and caspase-3 staining. Proliferation was not significantly different in COX-1+/+, COX-1+/−, and COX-1−/− animals. When susceptibility to UV-induced tumor formation was studied, tumor number, average tumor size, and time of tumor onset in COX-1−/− animals were identical to WT controls. Thus, enhanced apoptosis did not alter UV-induced skin carcinogenesis, suggesting other effects are key to nonsteroidal anti-inflammatory drug chemoprevention. These results contrast sharply with data obtained using the classic 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate cancer model in which a prominent protective effect of COX-1−/− is present. The lack of protection observed here confirms cancer mechanisms are distinct in UV- and tumor promotor-induced cancer models and indicates that chemoprevention strategies must specifically address cancer causes to be effective. |
| Databáze: | OpenAIRE |
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