"NKX2-1 and its downstream target, SCGB3A2: good cop or bad cop in lung cancer?" Shioko Kimura

Speaker: Dr. Shioko Kimura

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA

Title: NKX2-1 and its downstream target, SCGB3A2: good cop or bad cop in lung cancer?

Abstract: SCGB3A2, a member of the SCGB gene superfamily, is a downstream target for the homeodomain transcription factor, NKX2-1 that plays a role in organogenesis and regulation of gene expression in lung. NKX2-1 is a good diagnostic marker for lung adenocarcinomas routinely used at clinics. Its role in lung carcinogenesis is unfolding. SCGB3A2 consists of cytokine-like secreted proteins of small molecular weight (~10 kDa), and is predominantly expressed in lung airways. SCGB3A2 exhibits growth factor, anti-inflammatory, and anti-fibrotic activities, and can be used as a marker for lung cancer. We have recently identified that SCGB3A2 has anti-tumor activity using the Lewis Lung Carcinoma cells (LLC) lung metastasis model mouse, in which LLC cells were injected through the tail vein.  When mice received daily intravenous administration of SCGB3A2 for 6 days starting right after LLC injection, followed by necropsy on day 21, they showed a markedly reduced number and size of pulmonary surface tumors as compared to PBS-injected controls. Further, Scgb3a2-null mice when subjected to LLC lung metastasis model, developed considerably more pulmonary surface tumors. Taken together, these results revealed that SCGB3A2 exhibits anti-tumor activity. Various in vitro experiments demonstrated the involvement of JNK pathway in the anti-tumor activity of SCGB3A2. Additional experiments are under way to determine in more details the mechanism for the SCGB3A2 anti-tumor activity.

Host: 

Tadashi Yamamoto, Cell Signal Unit