Frequent decreased expression of candidate tumor suppressor gene, DEC1, and its anchorage-independent growth properties and impact on global gene expression in esophageal carcinoma.
Previous studies showed that expression of the novel candidate tumor suppressor gene, DEC1 (Deleted in Esophageal Cancer 1), is reduced in esophageal carcinoma and suppresses cancer cell growth in vitro and tumor growth in vivo in nude mice. This study shows that DEC1 gene expression was downregulated in 100% of 16 esophageal squamous cell carcinoma (ESCC) cell lines and 52 and 45%, respectively, of esophageal tumor specimens from Hong Kong and a high-risk ESCC region of Henan, China. Using epitope tagging, the DEC1 protein was localized to both the cytoplasm and nucleus of the cell. In 3D Matrigel culture, no significant difference in colony numbers formed was observed for DEC1 stable transfectants, as compared to vector-alone transfectant controls. However, significantly smaller colony sizes were observed for the DEC1 transfectants. In in vitro cell migration, invasion and soft agar assays of DEC1 transfectants, only the soft agar assay showed statistically significant differences in colony numbers with the vector-alone controls, indicating that DEC1 may be involved in anchorage-independent cell growth. In addition, the global gene expression affected by DEC1 in tumor-suppressive stable transfectants was investigated using cDNA oligonucleotide microarray hybridization. Three candidate genes, TFPI-2, GDF15 and DUSP6, were identified through this approach; they are downregulated in tumor segregants of DEC1 stable transfectants, ESCC cell lines and esophageal tumors and have a potential role in tumor growth and progression. These studies show that DEC1 is involved in esophageal cancer development and help elucidate its functional role in tumor development.
Leung
Alfred Chi Chung
AC
Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Hong Kong (SAR), People's Republic of China.
Wong
Victor Chun Lam
VC
Yang
Li Chun
LC
Chan
Pui Ling
PL
Daigo
Yataro
Y
Nakamura
Yusuke
Y
Qi
Robert Z
RZ
Miller
Lance David
LD
Liu
Edison Tak-Bun
ET
Wang
Li Dong
LD
Li
Ji-Lin
JL
Law
Simon
S
Tsao
Sai Wah
SW
Lung
Maria Li
ML
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C403671:DELEC1 protein, human; D025521:Tumor Suppressor Proteins