Primary wild type and COX-2-/- keraticytes were transfected with a retrovirus containing v-H-ras and the transfected keratinocytes grafted on to the backs of athymic nude mice. Tumor incidence and tumor size resulting from transfected COX-2 -/- keratinocytes was markedly reduced compared to tumors produced by transfected wild type keratinocytes. Lower proliferation rates and higher levels of terminal differentiation were observed in papillomas derived from the COX-2 -/- keratinocytes compared to papillomas derived from wild type keratinocytes. The levels of Ras expression were similar in both wild type and COX-2-/- tumor cells, however, the levels of p-EGFR and p-ERK1/2 were lower in papillomas derived from COX-2-/- keratinocytes compared to papillomas derived from wild type keratinocytes indicating that COX-2 deficiency decreased growth promoting signaling pathways down stream of v-H-Ras. The extents of vascularization and the levels of apoptosis were similar in wild type and COX-2-/- tumors, indicating that neither was not a factor in reducing COX-2-/- tumor size. . Thus, the deficiency of COX-2 in the transformed keratinocyte itself was sufficient to decrease tumor growth independent of systemic COX-2 expression.

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Lao, Huei-Chen; Akunda, Jacqueline K; Chun, Kyung-Soo et al. (2012) Genetic ablation of cyclooxygenase-2 in keratinocytes produces a cell-autonomous defect in tumor formation. Carcinogenesis 33:2293-300
Trempus, Carol S; Wei, Sung-Jen; Humble, Margaret M et al. (2011) A novel role for the T-box transcription factor Tbx1 as a negative regulator of tumor cell growth in mice. Mol Carcinog 50:981-91
Iguchi, Genzo; Chrysovergis, Kali; Lee, Seong-Ho et al. (2009) A reciprocal relationship exists between non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) and cyclooxygenase-2. Cancer Lett 282:152-8