- Research Article
- Open Access
siRNA-mediated silencing of the 37/67-kDa high affinity laminin receptor in Hep3B cells induces apoptosis
Cellular & Molecular Biology Letters volume 13, pages452–464 (2008)
The laminin-binding protein, variously called the 37/67-kDa high affinity laminin receptor or p40, mediates the attachment of normal cells to the laminin network, and also has a role as a ribosomal protein. Over-expression of this protein has been strongly correlated with the metastatic phenotype. However, few studies have investigated the cellular consequence of the ablation of this gene’s expression. To address this issue, the expression of the 37/67-kDa high affinity laminin receptor was knocked out with several siRNA constructs via RNA interference in transformed liver (Hep3B) cells. In each case where the message was specifically ablated, apoptosis was induced, as determined by annexin V/propidium iodide staining, and by double staining with annexin V and an antibody directed against the 37/67-kDa high affinity laminin receptor. These results suggest that this protein plays a critical role in maintaining cell viability.
glyceraldehyde 3-phosphate dehydrogenase
laminin-binding protein precursor p40
laminin receptor precursor
- PrPc :
cellular prion protein
small interfering RNAs
37-kDa laminin binding protein
67-kDa laminin receptor
Lesot, H., Kuhl, U. and Mark, K.V. Isolation of a laminin-binding protein from muscle cell membranes. EMBO J. 2 (1983) 861–865.
Malinoff, H.L. and Wicha, M.S. Isolation of a cell surface receptor protein for laminin from murine fibrosarcoma cells. J. Cell Biol. 96 (1983) 1475–1479.
Rao, N.C., Barsky, S.H., Terranova, V.P. and Liotta, L.A. Isolation of a tumor cell laminin receptor. Biochem. Biophys. Res. Commun. 111 (1983) 804–808.
Rao, C.N., Castronovo, V., Schmitt, M.C., Wewer, U.M., Claysmith, A.P., Liotta, L.A. and Sobel, M.E. Evidence for a precursor of the high-affinity metastasis-associated murine laminin receptor. Biochemistry 28 (1989) 7476–7486.
Yow, H.K., Wong, J.M., Chen, H.S., Lee, C.G., Davis, S., Steele, G.D., Jr. and Chen, L.B. Increased mRNA expression of a laminin-binding protein in human colon carcinoma: complete sequence of a full-length cDNA encoding the protein. Proc. Natl. Acad. Sci. USA 85 (1988) 6394–6398.
Tohgo, A., Takasawa, S., Munakata, H., Yonekura, H., Hayashi, N. and Okamoto, H. Structural determination and characterization of a 40-kDa protein isolated from rat 40 S ribosomal subunit. FEBS Lett. 340 (1994) 133–138.
Auth, D. and Brawerman, G. A 33-kDa polypeptide with homology to the laminin receptor: component of translation machinery. Proc. Natl. Acad. Sci. USA 89 (1992) 4368–4372.
Sato, M., Kinoshita, K., Kaneda, Y., Saeki, Y., Iwamatsu, A. and Tanaka, K. Analysis of nuclear localization of laminin binding protein precursor p40 (LBP/p40). Biochem. Biophys. Res. Commun. 229 (1996) 896–901.
Mecham, R.P., Hinek, A., Griffin, G.L., Senior, R.M. and Liotta, L.A. The elastin receptor shows structural and functional similarities to the 67-kDa tumor cell laminin receptor. J. Biol. Chem. 264 (1989) 16652–16657.
McCaffery, P., Neve, R.L. and Drager, U.C. A dorso-ventral asymmetry in the embryonic retina defined by protein conformation. Proc. Natl. Acad. Sci. USA 87 (1990) 8570–8574.
Rieger, R., Edenhofer, F., Lasmezas, C.I. and Weiss, S. The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nat. Med. 3 (1997) 1383–1388.
Gauczynski, S., Peyrin, J.M., Haik, S., Leucht, C., Hundt, C., Rieger, R., Krasemann, S., Deslys, J.P., Dormont, D., Lasmezas, C.I. and Weiss, S. The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J. 20 (2001) 5863–5875.
Gauczynski, S., Nikles, D., El-Gogo, S., Papy-Garcia, D., Rey, C., Alban, S., Barritault, D., Lasmezas, C.I. and Weiss, S. The 37-kDa/67-kDa laminin receptor acts as a receptor for infectious prions and is inhibited by polysulfated glycanes. J. Infect. Dis. 194 (2006) 702–709.
Ludewigs, H., Zuber, C., Vana, K., Nikles, D., Zerr, I. and Weiss, S. Therapeutic approaches for prion disorders. Expert Rev. Anti. Infect. Ther. 5 (2007) 613–630.
Vana, K., Zuber, C., Nikles, D. and Weiss, S. Novel aspects of prions, their receptor molecules, and innovative approaches for TSE therapy. Cell. Mol. Neurobiol. 27 (2007)107–128.
Zuber, C., Ludewigs, H. and Weiss, S. Therapeutic approaches targeting the prion receptor LRP/LR. Vet. Microbiol. 123 (2007) 387–393.
Wang, K.S., Kuhn, R.J., Strauss, E.G., Ou, S. and Strauss, J.H. High-affinity laminin receptor is a receptor for Sindbis virus in mammalian cells. J. Virol. 66 (1992) 4992–5001.
Thepparit, C. and Smith, D.R. Serotype-specific entry of dengue virus into liver cells: identification of the 37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor. J. Virol. 78 (2004) 12647–12656.
Akache, B., Grimm, D., Pandey, K., Yant, S.R., Xu, H. and Kay, M.A. The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9. J. Virol. 80 (2006) 9831–9836.
Coggin, J.H. Jr., Barsoum, A.L. and Rohrer, J.W. 37 kiloDalton oncofetal antigen protein and immature laminin receptor protein are identical, universal T-cell inducing immunogens on primary rodent and human cancers. Anticancer Res. 19 (1999) 5535–5542.
Zelle-Rieser, C., Barsoum, A.L., Sallusto, F., Ramoner, R., Rohrer, J.W., Holtl, L., Bartsch, G., Coggin, J.J. and Thurnher, M. Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma. J. Urol. 165 (2001) 1705–1709.
Castronovo, V. Laminin receptors and laminin-binding proteins during tumor invasion and metastasis. Invasion Metastasis 13 (1993) 1–30.
Castronovo, V., Claysmith, A.P., Barker, K.T., Cioce, V., Krutzsch, H.C. and Sobel, M.E. (1991). Biosynthesis of the 67 kDa high affinity laminin receptor. Biochem. Biophys. Res. Commun. 177 (1991) 177–183.
Buto, S., Tagliabue, E., Ardini, E., Magnifico, A., Ghirelli, C., van den Brule, F., Castronovo, V., Colnaghi, M.I., Sobel, M.E. and Menard, S. Formation of the 67-kDa laminin receptor by acylation of the precursor. J. Cell. Biochem. 69 (1998) 244–251.
Narumi, K., Inoue, A., Tanaka, M., Isemura, M., Shimo-Oka, T., Abe, T., Nukiwa, T. and Satoh, K. Inhibition of experimental metastasis of human fibrosarcoma cells by anti-recombinant 37-kDa laminin binding protein antibody. Jpn. J. Cancer Res. 90 (1999) 425–431.
Kaneda, Y., Kinoshita, K., Sato, M., Saeki, Y., Yamada, R., Wataya-Kaneda, M., and Tanaka, K. The induction of apoptosis in HeLa cells by the loss of LBP-p40. Cell Death Differ. 5 (1998) 20–28.
Leucht, C., Simoneau, S., Rey, C., Vana, K., Rieger, R., Lasmezas, C.I. and Weiss, S. The 37 kDa/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells. EMBO Rep. 4 (2003) 290–295.
Leucht, C., Vana, K., Renner-Muller, I., Dormont, D., Lasmezas, C.I., Wolf, E. and Weiss, S. Knock-down of the 37-kDa/67-kDa laminin receptor in mouse brain by transgenic expression of specific antisense LRP RNA. Transgenic Res. 13 (2004) 81–85.
Ardini, E., Pesole, G., Tagliabue, E., Magnifico, A., Castronovo, V., Sobel, M.E., Colnaghi, M.I. and Menard, S. The 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution. Mol. Biol. Evol. 15 (1998) 1017–1025.
Knowles B.B., Howe, C.C. and Aden D.P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209 (1980) 497–499.
Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411 (2001) 494–498.
Hannon, G.J. RNA interference. Nature 418 (2002) 244–251.
Hurtado, A., Tseng, J.C. and Meruelo, D. Gene therapy that safely targets and kills tumor cells throughout the body. Rejuvenation Res. 9 (2006) 36–44.