INCREASED TRANSFORMING GROWTH-FACTOR-ALPHA LEVELS IN HUMAN COLON-CARCINOMA CELL-LINES OVER-EXPRESSING PROTEIN-KINASE-C

Citation
P. Maruvada et Ae. Levine, INCREASED TRANSFORMING GROWTH-FACTOR-ALPHA LEVELS IN HUMAN COLON-CARCINOMA CELL-LINES OVER-EXPRESSING PROTEIN-KINASE-C, International journal of cancer, 80(1), 1999, pp. 72-77
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
ISSN journal
0020-7136
Volume
80
Issue
1
Year of publication
1999
Pages
72 - 77
Database
ISI
SICI code
0020-7136(1999)80:1<72:ITGLIH>2.0.ZU;2-O
Abstract
Transforming growth factor-alpha (TGF-alpha) is synthesized as a membr ane-bound precursor protein, pro-TGF-alpha, that is converted to a sol uble form by 2 endoproteolytic cleavages. Several factors have been im plicated in the regulation of the second rate-limiting step, including protein kinase C (PKC). Earlier results indicated a potential role fo r the conventional class of PKC isozymes in the observed increase in T GF-alpha in the conditioned media of 2 human colon carcinoma cell line s. The present study addresses the potential role of specific PKC isoz ymes 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- alpha, -beta I or -beta II; and the secretion of TGF-alpha into the co nditioned medium was determined. Over-expression of either PKC-PI or P KC-beta II in these cell lines enhanced the levels of TGF-alpha in the media 2- to 5-fold. Over-expression of PKC-alpha did not alter the am ount of TGF-alpha in the media to a significant extent. Transfection o f HCT 116 cells with the anti-sense PKC-beta I cDNA resulted in a redu ction in PKC-beta I protein expression. This was accompanied by a decr ease in the amount of TGF-alpha in the conditioned media. Our results indicate that modulation of PKC-beta protein levels alters the amount of TGF-alpha found in the conditioned media from these colon carcinoma cells. (C) 1999 Wiley-Liss, Inc.