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Amphiregulin anti‐sense oligodeoxynucleotides inhibit growth and transformation of a human colon carcinoma cell line
Author(s) -
Normanno Nicola,
Selvam Mouna P.,
Bianco Caterina,
Damiano Vincenzo,
de Angelis Ernesto,
Grassi Michele,
Magliulo Gabriella,
Tortora Giampaolo,
Salomon David S.,
Ciardiello Fortunato
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910620619
Subject(s) - amphiregulin , epidermal growth factor , cell growth , cell culture , microbiology and biotechnology , growth factor , malignant transformation , oligonucleotide , growth inhibition , transforming growth factor , biology , sense (electronics) , tgf alpha , chemistry , cancer research , biochemistry , receptor , dna , genetics
Amphiregulin (AR) is a secreted heparin‐binding growth factor that is structurally and functionally related to epidermal growth factor (EGF) and transforming growth factor a (TGFα). GEO cells are from a human colon cancer cell line that expresses high levels of AR protein and mRNA. To assess the role of AR in colon‐cancer cell proliferation and transformation, 2 different anti‐sense 20‐mer phosphorothioate oligodeoxy‐nucleotides (AR AS‐1 and AR AS‐2 S‐oligos) complementary to the 5′ sequence of AR mRNA were synthesized. Both AR AS S‐oligos were able to inhibit the anchorage‐dependent growth (ADG) of GEO cells. The 2 AR AS S‐oligos were equipotent when used in equimolar concentrations. In particular, a 40% growth inhibition was observed at a concentration of 10 μM, while a mis‐sense S‐oligo used as control had no effect on GEO cell growth. The AR AS‐1 S‐oligo used at the same concentration also inhibited by 40% the 3 H‐thymidine incorporation by DNA of GEO cells. The anchorage‐independent growth (AIG) of GEO cells was even more significantly affected by AR AS S‐oligo treatment. In fact, up to 80% inhibition of the AIG of GEO cells was observed when cells were treated with 10 μM of both AR AS S‐oligos. Finally, the AR AS S‐oligos were able to specifically inhibit AR protein expression in GEO cells, as assessed by immunocytochemistry. These data suggest that AR is involved in colon‐cancer cell transformation, and that AR may represent a suitable target for gene therapy in human colon carcinomas. © 1995 Wiley‐Liss, Inc.