Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Delayed diagnosis may result in progression and metastasis. Markers for early detection of RCC are lacking. The ATP-binding cassette transporter D1 (ABCD1) is located in the human peroxisome membrane. Its mutation causes X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disorder affecting lipid storage. The role of ABCD1 in human renal tumorigenesis was unclear. In this study, three pairs of RCC tissues were examined by cDNA microarray and data suggested that ABCD1 mRNA is downregulated. Downregulation of ABCD1 expression was confirmed by real-time PCR. ABCD1 expression was also downregulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. ABCD1 mRNA and protein expression levels assessed by immunohistochemistry in the RCC tissues were similar between genders, tumor grades, and tumor stages. Immunohisto-chemical assays also showed that ABCD1 expression was significantly higher in normal than in cancerous tissues (p<0.001). ABCD1 downregulation may be involved in human renal tumorigenesis.
SkatesS., IliopoulosO.Molecular markers for early detection of renal carcinoma: investigative approach. Clin Cancer Res2004; 10: 6296–301.
5.
BuiM.H., ZismanA., PantuckA.J., HanK.R., WiederJ., BelldegrunA.S.Prognostic factors and molecular markers for renal cell carcinoma. Expert Rev Anticancer Ther2001; 1: 565–75.
6.
HinoO., KobayashiT., MomoseS., KikuchiY., AdachiH., OkimotoK.Renal carcinogenesis: genotype, phenotype and dramatype. Cancer Sci2003; 94: 142–7.
7.
StorkelS., EbleJ.N., AdlakhaK.Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer1997; 80: 987–9.
MerseburgerA.S., HennenlotterJ., SimonP.Membranous expression and prognostic implications of epidermal growth factor receptor protein in human renal cell cancer. Anticancer Res2005; 25: 1901–7.
10.
KirkaliG., TuzelE., GulerC., GezerS., KirkaliZ.Significance of tissue laminin P(1) elastase and fibronectin levels in transitional cell carcinoma of the bladder. Eur Urol2001; 39: 292–9.
11.
SejimaT., MiyagawaI.Expression of bcl-2, p53 oncoprotein, and proliferating cell nuclear antigen in renal cell carcinoma. Eur Urol1999; 35: 242–8.
12.
HigginsC.F.ABC transporters: from microorganisms to man. Annu Rev Cell Biol1992; 8: 67–113.
TanakaA.R., TanabeK., MoritaM.ATP binding/hydrolysis by and phosphorylation of peroxisomal ATP-binding cassette proteins PMP70 (ABCD3) and adrenoleukodystrophy protein (ABCD1). J Biol Chem2002; 277: 40142–7.
15.
Lombard-PlatetG., SavaryS., SardeC.O., MandelJ.L., ChiminiG.A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern. Proc Natl Acad Sci U S A1996; 93: 1265–9.
16.
SteinbergS.J., KempS., BraitermanL.T., WatkinsP.A.Role of very-long-chain acyl-coenzyme A synthetase in X-linked adrenoleukodystrophy. Ann Neurol1999; 46: 409–12.
17.
KempS., PujolA., WaterhamH.R.ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum Mutat2001; 18: 499–515.
18.
KempS., WeiH.M., LuJ.F.Gene redundancy and pharmacological gene therapy: implications for X-linked adrenoleukodystrophy. Nat Med1998; 4: 1261–8.
19.
FuhrmanS.A., LaskyL.C., LimasC.Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol1982; 6: 655–63.
20.
GreeneF.L., PageD.L., FlemingI.D.AJCC Cancer Staging Manual, 6th ed. New York: Springer-Verlag, 2002; 323–328.
21.
HirschF.R., Varella-GarciaM., BunnP.A.Jr. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol2003; 21: 3798–807.
22.
AubourgP.On the front of X-linked adrenoleukodystrophy. Neurochem Res1999; 24: 515–20.
23.
LauerC., VolklA., RiedlS., FahimiH.D., BeierK.Impairment of peroxisomal biogenesis in human colon carcinoma. Carcinogenesis1999; 20: 985–9.
24.
MoserH.W.Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain1997; 1485–508.
25.
CiminiA., BernardoA., CifoneM.G., DiM.L., DiL.S.TNFalpha downregulates PPARdelta expression in oligodendrocyte progenitor cells: implications for demyelinating diseases. Glia2003; 41: 3–14.
26.
SzlosarekP., CharlesK.A., BalkwillF.R.Tumour necrosis factor-alpha as a tumour promoter. Eur J Cancer2006; 42: 745–50.
27.
SeelyJ.C., HasemanJ.K., NyskaA., WolfD.C., EverittJ.I., HaileyJ.R.The effect of chronic progressive nephropathy on the incidence of renal tubule cell neoplasms in control male F344 rats. Toxicol Pathol2002; 30: 681–6.
28.
IkemotoS., NaritaK., YoshidaN.Effects of tumor necrosis factor alpha in renal cell carcinoma. Oncol Rep2003; 10: 1947–55.
29.
FalkensammerC., JohrerK., GanderH.IL-4 inhibits the TNF-alpha induced proliferation of renal cell carcinoma (RCC) and cooperates with TNF-alpha to induce apoptotic and cytokine responses by RCC: implications for antitumor immune responses. Cancer Immunol Immunother2006; 55: 1228–37.
30.
IkemotoS., NaritaK., YoshidaN.Effects of tumor necrosis factor alpha in renal cell carcinoma. Oncol Rep2003; 10: 1947–55.
31.
KooA.S., ChiuR., SoongJ., DekernionJ.B., BelldegrunA.The expression of C-jun and junB mRNA in renal cell cancer and in vitro regulation by transforming growth factor beta 1 and tumor necrosis factor alpha 1. J Urol1992; 148: 1314–8.
32.
OyaM., HoriguchiA., MizunoR., MarumoK., MuraiM.Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma. Clin Cancer Res2003; 9: 1021–7.
