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Differential function of STAT5 isoforms in head and neck cancer growth control
- Source :
- Oncogene. 21:2846-2853
- Publication Year :
- 2002
- Publisher :
- Springer Science and Business Media LLC, 2002.
-
Abstract
- Up-regulation of the epidermal growth factor receptor (EGFR) is critical for the loss of growth control in a variety of human cancers, including squamous cell carcinoma of the head and neck (SCCHN). Stimulation of EGFR results in activation of mitogenic signaling pathways including Signal Transducers and Activators of Transcription (STATs). Stat5 activation has been primarily demonstrated in hematopoietic malignancies. Gene disruption studies suggest potentially distinct functions of the Stat5 isoforms, Stat5a and Stat5b, which are encoded by two genes closely linked on human chromosome 17. To determine the function of Stat5 in SCCHN growth control, we studied the expression and constitutive activation of Stat5a and Stat5b in normal and transformed human squamous epithelial cells. Increased constitutive activation of Stat5 was detected in transformed compared with normal squamous cells. Blockade of TGF-alpha or EGFR, abrogated Stat5 activation. Targeting of Stat5b using antisense oligonucleotides inhibited SCCHN growth. In addition, SCCHN cells stably transfected with dominant negative mutant Stat5b failed to proliferate in vitro. In contrast, targeting of Stat5a using either antisense or dominant negative strategies had no effect on cell growth. These results suggest that TGF-alpha/EGFR-mediated autocrine growth of transformed epithelial cells is dependent on activation of Stat5b but not Stat5a.
- Subjects :
- Gene isoform
Cancer Research
animal structures
STAT5B
STAT5 Transcription Factor
Tumor Cells, Cultured
Genetics
Humans
Protein Isoforms
Epidermal growth factor receptor
Autocrine signalling
Molecular Biology
STAT5
Cell Line, Transformed
biology
Cell growth
Tumor Suppressor Proteins
food and beverages
Transfection
Transforming Growth Factor alpha
Milk Proteins
DNA-Binding Proteins
ErbB Receptors
stomatognathic diseases
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Trans-Activators
Cancer research
biology.protein
Signal transduction
Cell Division
Signal Transduction
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....3df2884e735d8db3f9c38d191e133518