In vitro secretion of transforming growth factor alpha (TGF-α): A comparison of the A431 cell line with three human oesophageal squamous cell carcinoma lines

1992 ◽  
Vol 12 (4) ◽  
pp. 293-302 ◽  
Author(s):  
A. L. Thornley ◽  
G. J. Jones

Transforming growth factor alpha (TGF-α) is a single chain polypeptide which exists in a variety of forms differing in molecular weight. These forms are variously present in normal and neoplastic cells. Of particular interest are TGF-α's well-known mitogenic properties. The transition from a normal to a neoplastic cellular state results from signalling defects that may depend upon, iter alia, abonormal levels of expression and secretion of TGF-α. It is known that the secretion of TGF-α may be enhanced appreciably by agents such as phorbol 12-myristate 13-acetate (PMA), serum factors and epidermal growth factor (EGF). Here, we compare the efficacy of these three agents in the elevation of TGF-α secretion in the well studied A431 cell line with their previously undocumented efficacy in certain interesting, but little known, human oesophageal squamous cell carcinoma (SCC) lines.

1993 ◽  
Vol 13 (5) ◽  
pp. 303-312 ◽  
Author(s):  
Gregory J. Jones ◽  
Nina S. Heiss ◽  
Robin B. Veale ◽  
Alan L. Thornley

We have previously shown that four human oesophageal squamous cell carcinoma (SCC) cell lines secrete significant quantities of transforming growth factor alpha (TGF-α) in vitro. Three of these lines are known to produce supernumary low-affinity epidermal growth factor receptors (EGF-Rs). Using an125I-EGF compeitive binding assay and Scatchard analysis, we show that the fourth also overproduces low-affinity receptors. According to slot blot DNA analyses, the secretion of high levels of TGF-α is not associated with amplification of the TGF-α gene, and hyperproduction of the EGF-R is correlated with receptor gene amplification. Western blot analyses show that the c-Myc protein is overexpressed in two of the cell lines; and Southern and Northern blot analyses indicate that this overexpression occurs independently of c-myc gene amplification. Our results are consistent with an autocrine role for TGF-α and EGF-R in oesophageal carcinogenesis and support the possibility that c-myc overexpression may be required for the in vivo tumourigenicity of cells that produce high levels of TGF-α and the EGF-R.


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