Patterns of expression of lineage-specific markers during the in vitro-induced differentiation of HT29 colon carcinoma cells.
The four different cell types present in the mature colon, absorptive enterocytes, mucus-secreting goblet cells, Paneth cells, and enteroendocrine cells, are believed to derive from a common precursor, the stem cell, anchored near the base of the crypt. Stem cell descendants undergo several rounds of cell division, creating a pool of transit cells that are committed to differentiation. The mechanisms by which committed cells are allocated to the different cell lineages of the intestine are poorly understood. We have used the colon carcinoma cell line HT29 and Cl.16E cells, a clonal derivative of HT29 cells, to investigate the regulation and pattern of expression of several markers (MUC2, MUC3, carcinoembryonic antigen, and alkaline phosphatase) that are associated with a more differentiated phenotype and that, in the mature cells, are lineage restricted. HT29 cells can express, upon exposure to the appropriate inducers, distinct intestinal specific markers; they are, therefore, considered multipotent, similar to the stem cells of the crypt. Conversely, Cl.16E cells are lineage restricted and respond to cell contact inhibition by expressing a fully differentiated goblet cell phenotype. We show that, in HT29 cells, different inducers (12-O-tetradecanoylphorbol-13-acetate, forskolin, and sodium butyrate) modulate specific sets of markers. Forskolin induces the expression of both MUC2 and MUC3, whereas 12-O-tetradecanoylphorbol-13-acetate is capable of inducing only MUC2, and sodium butyrate, only MUC3 gene expression. Carcinoembryonic antigen, a marker common to enterocytes and goblet cells; can be induced by all the agents, whereas the alkaline phosphatase gene, the expression of which is characteristic of enterocytes, is responsive solely to sodium butyrate treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Velcich
A
A
Department of Oncology, Albert Einstein Cancer Center, Bronx, New York 10467, USA.
Palumbo
L
L
Jarry
A
A
Laboisse
C
C
Racevskis
J
J
Augenlicht
L
L
D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015415:Biomarkers; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics; D002277:Carcinoma / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D055262:Mucin-2; D055263:Mucin-3; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015415:Biomarkers; D002087:Butyrates; D002272:Carcinoembryonic Antigen; C524625:MUC2 protein, human; D055262:Mucin-2; D055263:Mucin-3; D009077:Mucins; D009363:Neoplasm Proteins; D020148:Butyric Acid; D005576:Colforsin; D000469:Alkaline Phosphatase; D013755:Tetradecanoylphorbol Acetate