The C-terminal 26-residue peptide of serpin A1 stimulates proliferation of breast and liver cancer cells: role of protein kinase C and CD47.
C26, the C-terminal 26 residue peptide of serpin A1, significantly increased cell proliferation in cultures of hepatoma cells, but not in porcine kidney epithelial cells, human skin fibroblasts or keratinocytes. The mitogenic activity of C26 was preferentially inhibited with a protein kinase C (PKC) inhibitor, an antibody against CD47 and CD47 short interfering RNA. The mutant C26-K19R,N22M, imitating a thrombospondin-like cell adhesion motif, increased the mitogenic activity in both Hep G2 cells and MCF-7 breast cancer cells. Phosphorylation of C26 at T24 (a putative PKC phosphorylation site) resulted in a 1.9-2.5 increase in mitogenic activity over C26 in MCF-7 cells.
Congote
Luis Fernando
LF
Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, ouest, Montreal, Que., Canada H3A 1A1. luis.f.congote@muhc.mcgill.ca
Temmel
Nyssa
N
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology*; D051928:CD47 Antigen; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000494:pharmacology*
D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D011493:Protein Kinase C