We have continued our efforts to develop in vivo and in vitro models to better understand the mechanistic role of genes highly differentially expressed in lung cancers. We have generated transgenic mice carrying a gene, PGP9.5, which is often over expressed in lung cancers. We are collaborating with Dr. Ilona Linnoila's laboratory to examine these transgenic animals for transgene expression as well as potential tumor formation, life span changes, and to breed them with other lung cancer animal models. We have identified two founder animals that carry lung specific expression of the PGP9.5 gene. These animals are now being bred for Dr. Linnoila's laboratory as an collaboration to address the role of PGP9.5 over expression in lung epithelium to EMU induced lung carcinogenesis. Our second line of study involving functional analysis of SMAD6 protein that often shows reduced expression in lung cancers. Using immunohistochemical analysis we showed that SMAD6 expression in lung tumors is associated with an increased rate of tumor recurrence in adenocarcinomas. We propose that this is due to reduction if negative growth signaling by TGF-beta/BMP upon SMAD6 expression. We are using siRNA approach to determine if SMAD6 inactivation would lead to reduction in cell growth. We are also using modeling systems to determine if the presence of SMAD6 contribute to tumor genesis.
| Hong, Kyeong-Man; Yang, Sei-Hoon; Chowdhuri, Sinchita Roy et al. (2007) Inactivation of LLC1 gene in nonsmall cell lung cancer. Int J Cancer 120:2353-8 |
| He, Ping; Varticovski, Lyuba; Bowman, Elise D et al. (2004) Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Hum Pathol 35:1196-209 |
| Monitto, Constance L; Dong, Seung-Myung; Jen, Jin et al. (2004) Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia. Clin Cancer Res 10:5862-9 |
| Krop, Ian; Player, Audrey; Tablante, Ana et al. (2004) Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Mol Cancer Res 2:489-94 |
| Player, Audrey; Gillespie, John; Fujii, Takeshi et al. (2003) Identification of TDE2 gene and its expression in non-small cell lung cancer. Int J Cancer 107:238-43 |
