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P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 1
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P1.02-009 - KCTD11 methylation in non-adenocarcinoma lung cancer (ID 2582)
09:30 - 16:30 | Author(s): J. Ni
Lung cancer is the leading cause of cancer-related death worldwide. Nowdays, the histological subtypes of lung cancer and corresponding genetic polymorphisms play an important role in deciding the treatment options. KCTD11, a novel tumor suppressor, acts on antagonizing Hedgehog (Hh) signaling pathway . The deregulation of KCTD11 might activate glioma-associated oncogene homolog 1(Gli) transcription factors and lead to tumorigenesis. The present study was designed to analyze expression of the KCTD11 in different pathological lung cancer cell lines and lung cancer tissues, also the mechanism of KCTD11 inactivation and the possible affected downstream signal pathway.
Lung cancer cell lines and tissues were used to detect the expression of KCTD11. The clinical significance was analysed.Methylation detection was completed. KCTD11 vectors were transfected to squamous cell lung cancer cell lines to detect the Gli1 expression.
The expression of KCTD11 was detected in Small airway epithelial cell (SAEC) and 14 lung cancer cell lines. RT-PCR showed reduced expression in lung cancer cell lines, especially in small cell lung cancer cell (SCLC) lines and squamous cell lung cancer cell (SCC) lines compared with SAEC. In all 14 tested cell lines (5 adenocarcinoma, 2 large cell, 3 SCC and 4 SCLC), we found these CpG islands were densely methylated in 3 of 4 SCLC cell lines, 2 of 3 SCC cell lines and 1 of 2 large cell lung cancer (LCC) cell linesbut none of the 5 adenomacarcinoma cell lines and SAEC. TMA staining showed significantly lower expression of KCTD11 in SCC lung cancer tissues than in normal tissues (24.2% vs 87.5%, p=0.000) .Also 5 of 10 SCC tissues compared with 1 of 12 adenocarcinoma showed methylation status. IHC analysis showed that there was 44.1% (55/118) positive Gli1 expression in group of negative KCTD11 expression. Correlation analysis showed they might exist marginally negative correlation (r=-0.165, p=0.052). H2170 cell lines with KCTD11 plasmid transfection showed significantly reduced Gli-1 expression compared with control plasmid transfection. (picture 1) Figure 1
In summary, we found the reduced KCTD11 expression in lung cancer. Hypermethylation was the important mechanism of KCTD11 epigenetic change in non-adenocarcinoma lung cancer cell lines and tissues. KCTD11 silencing resulted in the high expression of Gli1, a downstream mediator of Hh signaling pathway, and might affected the tumorigenesis and development in lung cancer. Targeting the KCTD11 treatment and thus controlling the Hh pathway might a new treatment target in non-adenocarcinoma lung cancer.