We have previously demonstrated that beta-arrestin1 and 2 form complexes with various prostaglandin receptors during mouse skin tumor development (Chun et al., Carcinogenesis, 9:1620, 2009). Therefore, the goals of the present study were to elucidate the effects of beta-arrestin1 or 2 deficiency on mouse skin tumor development using the multi-stage mouse skin tumor model. Surprisingly, beta-arrestin 1 decreased the number and size of skin tumors using this model;whereas the deficiency of beta-arrestin2 did not effect the number of tumors but in fact significantly increased tumor size. Furthermore, while beta-arrestin1 deficiency decreased p-ERK1/2 and COX-2 induction, beta-arrestin2 deficiency increased p-ERK1/2 but had no effect on COX-2 expression. Further studies are underway to better elucidate the effects of beta-arrestin1 and 2 deficiency on the signaling pathways we have previously demonstrated to be involved in mouse skin tumor development. In the ovarian cancer studies, our results to date indicate that COX-1, but not COX-2, deficiency reduces mouse ovarian cancer development by about 50%.
|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|