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Downmodulation of TGF‐α protein expression with antisense oligonucleotides inhibits proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells
Author(s) -
Grandis Jennifer Rubin,
Chakraborty Arup,
Zeng Qing,
Melhem Mona F.,
Tweardy David J.
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19980401)69:1<55::aid-jcb6>3.0.co;2-u
Subject(s) - autocrine signalling , cell growth , transforming growth factor , cancer research , epidermal growth factor receptor , biology , head and neck squamous cell carcinoma , tgf alpha , receptor , cell , signal transduction , microbiology and biotechnology , cancer , endocrinology , head and neck cancer , biochemistry , genetics
Interruption of an autocrine growth pathway involving TGF‐α and EGFR may inhibit tumor growth and improve survival in head and neck cancer patients. We previously demonstrated that biopsy specimens and established cell lines from patients with squamous cell carcinoma of the head and neck (SCCHN) overexpress TGF‐α and its receptor, epidermal growth factor receptor (EGFR) at both the mRNA and protein levels. Protein localization studies showed that TGF‐α and EGFR are produced by the same epithelial cells in tissues from head and neck cancer patients further supporting a role for this ligand‐receptor pair in an autocrine growth pathway. To confirm that TGF‐α contributes to autocrine growth, we examined the effect of down regulation of TGF‐α protein on SCCHN cell proliferation. Treatment of 6 SCCHN cell lines with antisense oligodeoxynucleotides targeting the translation start site of human TGF‐α mRNA decreased TGF‐α protein production by up to 93% and reduced cell proliferation by a mean of 76.2% compared to a 9.7% reduction with sense oligonucleotide (range P<0R > = 0.036–0.0001). TGF‐α antisense oligonucleotide exposure also decreased TGF‐α protein levels in normal oropharyngeal mucosal epithelial cells, however their growth rate was not affected. These findings indicate that TGF‐α is participating in an autocrine signaling pathway in transformed, but not in normal mucosal epithelial cells, that promotes proliferation. J. Cell. Biochem. 69:55–62, 1998. © 1998 Wiley‐Liss, Inc.