title: Molecular regulation of intercellular adhesion molecule 1 (ICAM-1) expression in renal cell carcinoma.
abstract: Intercellular adhesion molecule-1 (ICAM-1) mediates two important functional aspects of tumor biology, namely enhancement of tumor metastasis and mediation of host defense mechanisms such as lymphocyte-mediated tumor cytotoxicity. Since ICAM-1 is expressed by most renal cell carcinomas (RCC), the regulation of ICAM-1 expression is important in understanding the biological behavior of RCC. We report an investigation on ICAM-1 expression and molecular regulation by cytokines and protein kinase C activator on RCC cell lines. Of the various cytokines, tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN gamma), and phorbol myristate acetate (PMA) strongly upregulated ICAM-1 protein expression on RCC. The kinetics of ICAM-1 message induction was studied by Northern analysis of total RNA extracted from RCC and normal kidney proximal tubular (NKPT) cells. Time course studies showed that ICAM-1 mRNA was upregulated by INF gamma, TNF alpha, and PMA, plateaued after 2 h, and remained increased for up to 24 h. Although ICAM-1 mRNA in NKPT cells was upregulated by these cytokines, their messages returned to basal levels after 24 h. ICAM-1 mRNA stability assays showed that both unstimulated and stimulated RCC cells had very stable ICAM-1 mRNA up to 24 h. In order to investigate whether increased gene transcription contributes to ICAM-1 upregulation, RCC cells were treated with TNF alpha, IFN gamma, or PMA with or without simultaneous addition of actinomycin D. ICAM-1 message induction-blocking studies suggested that primary upregulation of ICAM-1 mRNA may be caused by transcriptional upregulation. These results suggest that long-lasting ICAM-1 message upregulation in response to cytokines or PMA may be due to transcriptional upregulation in the early phase and stabilization of ICAM-1 message in the later phase (after 4 h). These observations suggest that RCC may lack the normal downregulatory mechanisms which control ICAM-1 expression and may explain the high frequency of ICAM-1 expression observed on primary human RCC.
authors.affiliation: Department of Urology, Tokyo Women's Medical College, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanabe
authors.forename: S C
authors.initials: SC
authors.lastname: Campbell
authors.forename: J P
authors.initials: JP
authors.lastname: Alexander
authors.forename: F
authors.initials: F
authors.lastname: Steinbach
authors.forename: M G
authors.initials: MG
authors.lastname: Edinger
authors.forename: R R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: A C
authors.initials: AC
authors.lastname: Novick
authors.forename: E A
authors.initials: EA
authors.lastname: Klein
mesh_terms: D002292:Carcinoma, Renal Cell; D016207:Cytokines / Q000494:pharmacology; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D011493:Protein Kinase C