@article {183, title = {Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e42264}, abstract = {

BACKGROUND: Gremlin, a member of the Dan family of BMP antagonists, is a glycosylated extracellular protein. Previously Gremlin has been shown to play a role in dorsal-ventral patterning, in tissue remodeling, and recently in angiogenesis. Evidence has previously been presented showing both over- and under-expression of Gremlin in different tumor tissues. Here, we sought to quantify expression of Gremlin in cancers of the lung and performed in vitro experiments to check whether Gremlin promotes cell growth and proliferation.

METHODOLOGY/PRINCIPAL FINDINGS: Expression of Gremlin in 161 matched tumor and normal lung cancer specimens is quantified by quantitative real-time PCR and protein level is measured by immunohistochemistry. GREM1 was transfected into lung fibroblast and epithelial cell lines to assess the impact of overexpression of Gremlin in vitro.

RESULTS: Lung adenocarcinoma but not squamous cell carcinoma shows a significant increase in Gremlin expression by mRNA and protein level. Lung fibroblast and epithelial cell lines transfected with GREM1 show significantly increased cell proliferation.

CONCLUSIONS/SIGNIFICANCE: Our data suggest that Gremlin acts in an oncogenic manner in lung adenocarcinoma and could hold promise as a new diagnostic marker or potential therapeutic target in lung AD or general thoracic malignancies.

}, keywords = {Adenocarcinoma, Cell Line, Tumor, Cell Proliferation, Epithelial Cells, Female, Fibroblasts, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Intercellular Signaling Peptides and Proteins, Lung Neoplasms, Male, Neoplasm Proteins, Real-Time Polymerase Chain Reaction, Respiratory Mucosa, RNA, Messenger, RNA, Neoplasm}, issn = {1932-6203}, doi = {10.1371/journal.pone.0042264}, author = {Mulvihill, Michael S and Kwon, Yong-Won and Lee, Sharon and Fang, Li Tai and Choi, Helen and Ray, Roshni and Kang, Hio Chung and Jiang-Hua Mao and Jablons, David and Kim, Il-Jin} }