Increased transforming growth factor-α levels in human colon carcinoma cell lines over-expressing protein kinase C
✍ Scribed by Padma Maruvada; Alan E. Levine
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 154 KB
- Volume
- 80
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Transforming growth factor-␣ (TGF-␣) is synthesized as a membrane-bound precursor protein, pro-TGF-␣, that is converted to a soluble form by 2 endoproteolytic cleavages. Several factors have been implicated in the regulation of the second rate-limiting step, including protein kinase C (PKC). Earlier results indicated a potential role for the conventional class of PKC isozymes in the observed increase in TGF-␣ in the conditioned media of 2 human colon carcinoma cell lines. The present study addresses the potential role of specific PKC isozymes in this process using sense and anti-sense expression vectors for PKC isozymes. Two human colon carcinoma cell lines, HCT 116 and GEO, were transfected with plasmids, leading to the over-expression of PKC-␣, -I or -II; and the secretion of TGF-␣ into the conditioned medium was determined. Over-expression of either PKC-I or PKC-II in these cell lines enhanced the levels of TGF-␣ in the media 2-to 5-fold. Over-expression of PKC-␣ did not alter the amount of TGF-␣ in the media to a significant extent. Transfection of HCT 116 cells with the anti-sense PKC-I cDNA resulted in a reduction in PKC-I protein expression. This was accompanied by a decrease in the amount of TGF-␣ in the conditioned media. Our results indicate that modulation of PKC- protein levels alters the amount of TGF-␣ found in the conditioned media from these colon carcinoma cells.