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Differential mucin expression in colon carcinoma HT‐29 clones with variable resistance to 5‐fluorouracil and methotrexate
Author(s) -
Leteurtre Emmanuelle,
Gouyer Valérie,
Rousseau Karine,
Moreau Odile,
Barbat Alain,
Swallow Dallas,
Huet Guillemette,
Lesuffleur Thécla
Publication year - 2004
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1016/j.biolcel.2003.12.005
Subject(s) - biology , methotrexate , fluorouracil , mucin , carcinoma , cancer research , colon carcinoma , immunology , chemotherapy , colorectal cancer , biochemistry , genetics , cancer
A current challenge is to define the biological characteristics of colon tumor cells resistant to chemotherapy. Distinct sub‐populations of mucus‐secreting cells were previously obtained from the colon cancer cell line HT‐29 after long‐term treatment with the anti‐cancer drugs, 5‐fluorouracil (5‐FU) and methotrexate (MTX). Since mucins are increasingly implicated as playing a role in carcinogenesis, we studied the pattern of mucin expression in two HT‐29 clones of mucus‐secreting and two clones of enterocyte‐like phenotype which differ in their capacity to resist to 5‐FU and/or MTX. The expression of both transmembrane (MUC1, MUC3, MUC4) and secreted gel‐forming (MUC2, MUC5AC, MUC5B, MUC6) mucins in clones was studied by northern and/or western blotting. The four HT‐29 clones showed three cellular phenotypes: (1) The mucus‐secreting clone HT29‐5F12 consists of unpolarized cells with mucus secretions that have anti‐colonic mucin immunoreactivity, and mainly expresses MUC2 and is resistant to 5‐FU and sensitive to MTX; (2) The mucus‐secreting clone HT29‐5M21 forms a monolayer of polarized cells with strong anti‐gastric mucin immunoreactivity and mainly expresses MUC5AC and MUC5B and is resistant to MTX and sensitive to 5‐FU; (3) The two enterocyte‐like clones, HT29‐5F7 and HT29‐5M12 are resistant to both MTX and 5‐FU and express mainly MUC1 and MUC5B, respectively. These clones which originate from a same colorectal tumour and display different patterns of mucin expression as well as differing resistance to MTX and 5‐FU will make useful in vitro models for studying the potential role of mucins or other biological markers in drug resistance pathways.