Involvement of protein kinase C and an elastase‐like enzyme in the processing of transforming growth factor‐α in human colon carcinoma cell lines

Levine, Alan E.

doi:10.1002/ijc.2910580121

Cited by 8 publications

(20 citation statements)

References 27 publications

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“…TPA treatment induces TGF-a in human keratinocytes (39,40) and colon carcinoma cell lines (41), and HB-EGF in rat aortic smooth muscle cells (42). In mouse skin, the induction of TGF-a and HB-EGF by tumor promoters correlates with sustenance of the proliferation of basal keratinocytes (29,43,44).…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Protein Kinase Cα in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis

et al. 2005

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We generated a mouse strain lacking protein kinase CA (PKCA) and evaluated the significance of the enzyme in epithelial hyperplasia and tumor formation. PKCA-deficient mice exhibited increased susceptibility to tumor formation in two-stage skin carcinogenesis by single application of 7,12-dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. Tumor formation was not enhanced by DMBA or TPA treatment alone, suggesting that PKCA suppresses tumor promotion. However, the severity of epidermal hyperplasia induced by topical TPA treatment was markedly reduced. In mutant mice, the number of 5-bromo-2V-deoxyuridine-labeled epidermal basal keratinocytes increased 16 to 24 hours after topical TPA treatment as in the case of wild-type mice, but significantly decreased at 36 and 48 hours. Furthermore, the regenerating epithelium induced by skin wound significantly decreased in thickness but was not structurally impaired. The enhanced tumor formation may not be associated with epidermal hyperplasia. The induction levels of epidermal growth factor (EGF) receptor ligands, tumor growth factor A (TGF-A), and heparin-binding EGF-like growth factor, in the skin of mutant mice by TPA treatment were significantly lower than those in the skin of wild-type mice. PKCA may regulate the supply of these EGF receptor ligands in basal keratinocytes, resulting in a reduced epidermal hyperplasia severity in the mutant mice. We propose that PKCA positively regulates epidermal hyperplasia but negatively regulates tumor formation in two-stage skin carcinogenesis. (Cancer Res 2005; 65(16): 7356-62)

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Section: Discussionmentioning

confidence: 99%

Deficiency of Protein Kinase Cα in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis

et al. 2005

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“…Recent work by our group has shown that the HCA-7 cells become polarized in culture and release prostaglandins in a vectorial fashion (30). The HCT-116 cells have been extensively characterized as well and these cells have been found to have a homozygous mutation at the hMLH1 locus and are poorly differentiated (24,(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2.

Sheng¹,

Shao²,

Kirkland³

et al. 1997

J. Clin. Invest.

666

435

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“…This media was collected, lyophilized and redissolved in PBS. Aliquots of this concentrated media were assayed for the presence of TGF-␣ using a commercial RIA kit (Biomedical Technologies, Inc., Stoughton, MA) following the manufacturer's protocol as previously described (Levine, 1994). The sensitivity of the procedure used was 20 pg/ml.…”

Section: Tgf-␣ Determinationmentioning

confidence: 99%

“…Brattain) were grown in McCoy's 5A medium (GIBCO-BRL, Grand Island, NY) containing 5% FBS (JRH Biosciences, Lenexa, KS) supplemented with vitamins, amino acids and antibiotics (Levine, 1994;Ramesh and Levine, 1995). Cells were plated (1 ϫ 10 6 cells) in 25-cm 2 flasks and grown to 40-60% confluence.…”

Section: Cell Culture and Transfection With Pkc-containing Plasmidsmentioning

confidence: 99%

“…The extracellular domains of the precursor proteins immediately preceding the transmembrane do-main are involved in regulation of the release process (Arribas et al, 1997). Our earlier studies addressed the role of PKC in pro-TGF-␣ processing using specific agonists and antagonists of PKC and indicated a potential involvement of conventional PKC isoforms in the processing of TGF-␣ in 2 colon carcinoma cell lines (Levine, 1994;Ramesh and Levine, 1995). In the present study, the role of PKC was examined directly by altering the level of protein expression of specific PKC isozymes by transfecting with vectors, leading to the over-expression of PKC-␣, -␤I or -␤II or the anti-sense expression of PKC-␤I.…”

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confidence: 99%

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Increased transforming growth factor-? levels in human colon carcinoma cell lines over-expressing protein kinase C

Maruvada

Levine

1999

Int. J. Cancer

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Transforming growth factor‐α (TGF‐α) is synthesized as a membrane‐bound precursor protein, pro‐TGF‐α, 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‐α 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‐α, ‐βI or ‐βII; and the secretion of TGF‐α into the conditioned medium was determined. Over‐expression of either PKC‐βI or PKC‐βII in these cell lines enhanced the levels of TGF‐α in the media 2‐ to 5‐fold. Over‐expression of PKC‐α did not alter the amount of TGF‐α in the media to a significant extent. Transfection of HCT 116 cells with the anti‐sense PKC‐βI cDNA resulted in a reduction in PKC‐βI protein expression. This was accompanied by a decrease in the amount of TGF‐α in the conditioned media. Our results indicate that modulation of PKC‐β protein levels alters the amount of TGF‐α found in the conditioned media from these colon carcinoma cells. Int. J. Cancer 80:72–77, 1999. © 1999 Wiley‐Liss, Inc.

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Involvement of protein kinase C and an elastase‐like enzyme in the processing of transforming growth factor‐α in human colon carcinoma cell lines

Cited by 8 publications

References 27 publications

Deficiency of Protein Kinase Cα in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis

Deficiency of Protein Kinase Cα in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis

Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2.

Increased transforming growth factor-? levels in human colon carcinoma cell lines over-expressing protein kinase C

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