Expression of carcinoembryonic antigen and related genes in lung and gastrointestinal cancers

Abstract

Carcinoembryonic antigen (CEA), a tumor marker for lung cancers of small cell (SCLC) and non-small cell (NSCLC) types, belongs in a multigene family which includes non-specific cross-reacting antigen (NCA) and biliary glycoprotein 1 (BGP). We used specific cDNA probes and a CEA immunoassay to determine the pattern of expression in normal and malignant lung and gastrointestinal (GI) tissues. Normal lung contained high amounts of NCA and a low concentration of CEA. All 3 genes were expressed discordantly in lung tumors and cell lines. In contrast, all three genes were expressed in most G1 tumor cell lines. In both lung and colorectal cell lines expression of NCA RNA was relatively high, while BGP RNA was relatively low, and the median concentrations of CEA were greater than in corresponding non-malignant tissues. While CEA protein concentrations in lung cell lines were similar to those present in G1 cell lines, the ratio of NCA:CEA RNA was significantly higher in lung cancer lines than in colorectal lines. Thus, NCA constitutes most of the "CEA-like" immunoreactivity previously described in lung cancers. There was excellent concordance between expression of CEA RNA and CEA protein, as well as between concentrations of CEA protein in cell line pellets and supernatant fluids. Of interest, significantly higher rates of CEA expression were present in lung cancers expressing neuroendocrine (NE) markers. The association between CEA expression and NE cell properties is intriguing and may prove to be of clinical interest.

Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis

“…Combination of subtractive hybridization and high-density cDNA microarrays has been well documented for identifying tumor speci®c genes in a variety of cancers (Kitahara et al, 2001). A good indication for the success of this approach is the fact that several of the genes including GRP, ASH1, TOP2A and CEA are known to be highly expressed in SCLC tumors (Ball et al, 1993;Giaccone, 1994;Kim et al, 1992;Yamaguchi et al, 1983). Another indication of the success of this approach was the identi®cation of a large number of genes that have been previously described to be associated with cancer.…”

Expression of Human MDGA1 Increases Cell Motility and Cell-Cell Adhesion and Reduces Adhesion to Extracellular Matrix Proteins in MDCK Cells

“…The presence of these structural features makes it a unique protein, as it is the first GPI-linked IgSF molecule containing a MAM domain described to our knowledge. Some of the GPIlinked IgSF proteins are involved in a variety of specific cell-cell interactions and/or in migration, such as LAMP, BIG-1, neurotrimin, CEPU-1, GP55 [7][8][9], CEA, CEACAM-6, NCAM p120 [10][11][12], F3/F11/contactin and TAG1/axonin-1 [13,14]. In addition, the presence of the MAM and/or Ig domains confers to these proteins the capacity to interact with other cells through homophilic and/or heterophilic interactions [2,4,15].…”

CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling

“…CEAs play a role in a number of normal and pathological processes, like control of granulocyte, dendritic cell, and T-cell activation (Kuijpers et al, 1992;Kammerer et al, 1998Kammerer et al, , 2001, regulation of differentiation, breast duct formation and angiogenesis (Huang et al, 1999;Ergun et al, 2000;Screaton et al, 2000). In the CEA subgroup, CEA (CEACAM5) and CEACAM6 (formerly nonspecific cross-reacting antigen) are overexpressed in a wide variety of epithelial malignancies (Kim et al, 1992), whereas CEACAM1 (formerly biliary glycoprotein) is usually downregulated (Neumaier et al, 1993). CEAs are widely used clinically as tumor markers, specifically for the detection of colorectal carcinoma after surgical resection (Chevinsky, 1991).…”