ABSTRACT
CD43 is a highly glycosylated transmembrane protein expressed on the surface of most hematopoietic cells. Expression of CD43 has also been demonstrated in many human tumor tissues, including colon adenomas and carcinomas, but not in normal colon epithelium. The potential contribution of CD43 to tumor development is still not understood. Here, we show that overexpression of CD43 increases cell growth and colony formation in mouse and human cells lacking expression of either p53 or ARF (alternative reading frame) tumor-suppressor proteins. In addition, CD43 overexpression also lowers the detection of the FAS death receptor on the cell surface of human cancer cells, and thereby helps to evade FAS-mediated apoptosis. However, when both p53 and ARF proteins are present, CD43 overexpression activates p53 and suppresses colony formation due to induction of apoptosis. These observations suggest CD43 as a potential contributor to tumor development and the functional ARF-p53 pathway is required for the elimination of cells with aberrant CD43 expression.
Subject(s)
Apoptosis/physiology , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p16/deficiency , Genes, p53 , Intercellular Signaling Peptides and Proteins/physiology , Leukosialin/physiology , Neoplasms/metabolism , Tumor Suppressor Protein p53/deficiency , fas Receptor/physiology , Animals , Apoptosis/genetics , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/physiology , HCT116 Cells , Humans , Intercellular Signaling Peptides and Proteins/genetics , Leukosialin/genetics , Mice , Neoplasms/pathology , Signal Transduction/geneticsABSTRACT
CD43 is an abundant transmembrane sialoglycoprotein in leukocyte-type cell lines, but it has also been suggested to be present in colon adenomas and colon carcinomas. We have now shown that CD43 is expressed in a variety of cell lines of different origins (CaSKI, A549, 293, MTSV1-7, MCF7, HT-1080, Jurkat, K562, COLO 205, HT-29, Caco-2, DLD-1 and SW480). The level of expression of CD43 mRNA was analyzed by reverse transcriptase-polymerase chain reaction and that of the protein by immunoprecipitation and Western blot, flow cytometry and confocal microscopy using two monoclonal anti-CD43 antibodies (L10 and 4D2). As all cell lines expressed CD43, it is suggested that CD43 has a more fundamental function than previously believed and thus cannot be considered only as a specific leukocyte marker.
Subject(s)
Antigens, CD , Sialoglycoproteins/biosynthesis , Antibodies, Monoclonal/metabolism , Blotting, Western , Cell Line , Cell Separation , Electrophoresis, Polyacrylamide Gel , Exons , Flow Cytometry , Humans , Introns , Jurkat Cells , Leukosialin , Microscopy, Confocal , Microscopy, Fluorescence , Plasmids/metabolism , Precipitin Tests , Reverse Transcriptase Polymerase Chain Reaction , Sialoglycoproteins/metabolism , Tumor Cells, CulturedABSTRACT
About a fifth of the human gene pool belongs largely either to Indo-European or Dravidic speaking people inhabiting the Indian peninsula. The 'Caucasoid share' in their gene pool is thought to be related predominantly to the Indo-European speakers. A commonly held hypothesis, albeit not the only one, suggests a massive Indo-Aryan invasion to India some 4,000 years ago [1]. Recent limited analysis of maternally inherited mitochondrial DNA (mtDNA) of Indian populations has been interpreted as supporting this concept [2] [3]. Here, this interpretation is questioned. We found an extensive deep late Pleistocene genetic link between contemporary Europeans and Indians, provided by the mtDNA haplogroup U, which encompasses roughly a fifth of mtDNA lineages of both populations. Our estimate for this split is close to the suggested time for the peopling of Asia and the first expansion of anatomically modern humans in Eurasia [4] [5] [6] [7] [8] and likely pre-dates their spread to Europe. Only a small fraction of the 'Caucasoid-specific' mtDNA lineages found in Indian populations can be ascribed to a relatively recent admixture.
