Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Inhibition of prostate tumor growth by overexpression of NudC, a microtubule motor-associated protein

Oncogene volume 23, pages 2499–2506 (2004)Cite this article

Abstract

Microtubules play a central role in coordinating various cellular functions that are orchestrated by their interaction with molecular motors. Anticancer drugs that target microtubule dynamics have been shown to be effective in cancer treatment. However, the effect of microtubule motor-associated molecules on cancer cell proliferation is not clear. Here, we investigated the role of NudC, a nuclear movement protein associated with the microtubule motor dynein, on prostate tumorigenesis. Recombinant adenovirus expressing NudC (Ad-NudC) was used to examine the effects of NudC on the tumorigenicity of prostate cancer cells. Expression of NudC in LNCaP cells inhibited their anchorage-independent growth in a soft agar colony assay. Expression of NudC in DU145 or PC-3 cells inhibited tumor growth in a subcutaneous xenograft model. At the cellular level, expression of NudC in DU145 and PC-3 cells inhibited cell proliferation at 48 h after Ad-NudC infection. FACS analysis of cell cycle distribution showed that 50–60% of Ad-NudC-infected PC-3 cells have a G2/M-phase DNA content compared to about 16–19% in Ad-Luciferase (Ad-Luc)-infected control cells, suggesting that NudC overexpression resulted in aberrant cell cycle progression. Immunofluorescence microscopy revealed a significant increase in cells with a single enlarged nucleus and cells exhibiting multiple nuclei, along with a concomitant increase in cell size in Ad-NudC-infected cells. These results suggest that NudC overexpression led to a block in cell division of prostate cancer cells, and that Ad-NudC may provide a new anticancer drug approach targeting the function of a microtubule motor-associated protein.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Angus SP, Fribourg AF, Markey MP, Williams SL, Horn HF, DeGregori J, Kowalik TF, Fikasawa K and Knudsen ES . (2002). Exp. Cell Res., 276, 201–213.

  • Aumais JP, Tunstead JR, McNeil R, Schaar B, McConnell SK, Lin S-H, Clark GD and Yu-Lee L-Y . (2001). J. Neurosci., 21, RC187–RC193.

  • Aumais JP, Tunstead JR, Morris SM and Yu-Lee L-Y . (2000). Mol. Biol. Cell, 11, 353a.

  • Aumais JP, Williams SN, Luo W, Nishino M, Caldwell KA, Caldwell GA, Lin S-H and Yu-Lee L-Y . (2003). J. Cell Sci., 116, 1991–2003.

  • Axtell SM, Truong TM, O'Neal KD and Yu-Lee L-Y . (1995). Mol. Endocrinol., 9, 312–318.

  • Baas PW . (1999). Neuron, 22, 23–31.

  • Banks JD and Heald R . (2001). Curr. Biol., 11, R128–R131.

  • Beaudouin J, Gerlich D, Daigle N, Eils R and Ellenberg J . (2002). Cell, 108, 83–96.

  • Bloom J and Pagana M . (2003). Semin. Cancer Biol., 13, 41–47.

  • Chen J-G and Horwitz SB . (2002). Cancer Res., 62, 1935–1938.

  • Chiu Y-H, Xiang X, Dawe AL and Morris NR . (1997). Mol. Biol. Cell, 8, 1735–1749.

  • Coquelle FM, Caspi M, Cordelieres FP, Dompierre JP, Dujardin DL, Koifman C, Martin P, Hoogenraad CC, Akhmanova A, Glajart N, De Mey JR and Reiner O . (2002). Mol. Cell. Biol., 22, 3089–3102.

  • Dujardin DL and Vallee RB . (2002). Curr. Op. Cell Biol., 14, 44–49.

  • Echeverri CJ, Paschal BM, Vaughan KT and Vallee RB . (1996). J. Cell Biol., 132, 617–633.

  • Estrera VT, Chen D-T, Luo W, Hixon DC and Lin S-H . (2001). J. Biol. Chem., 276, 15541–15553.

  • Faulkner NE, Dujardin DL, Tai C-Y, Vaughan KT, O'Connell CB, Wang Y-L and Vallee RB . (2000). Nat. Cell Biol., 2, 784–791.

  • Gartel AL and Tyner AL . (2002). Mol. Cancer Ther., 1, 639–649.

  • Giancotti FG and Ruoslahti E . (1990). Cell, 60, 849–859.

  • Gocke CD, Osmani SA and Miller BA . (2000a). Histochem. Cell Biol., 114, 293–301.

  • Gocke CD, Reaman GH, Stine C, Zhang M-Y, Osmani SA and Miller BA . (2000b). Leuk. Lymph., 39, 447–454.

  • Han G, Liu B, Zhang J, Zuo W, Morris NR and Xiang X . (2001). Curr. Biol., 11, 719–724.

  • Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA and Murphy GP . (1983). Cancer Res., 43, 1809–1818.

  • Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF and Jones LW . (1979). Invest. Urol., 17, 16–23.

  • Karki S and Holzbaur ELF . (1999). Curr. Op. Cell Biol., 11, 45–53.

  • Karki S, LaMonte B and Holzbaur ELF . (1998). J. Cell Biol., 142, 1023–1034.

  • Ligon LA, Spencer SS, Tokito M and Holzbaur ELF . (2003). Mol. Biol. Cell, 14, 1405–1417.

  • Lin S-H, Pu YS, Luo W, Wang Y and Logothetis CJ . (1999). Anticancer Res., 19, 337–340.

  • Miller BA, Zhang M-Y, Gocke CD, Souza CD, Osmani AH, Lynch C, Davies J, Bell L and Osmani SA . (1999). Exp. Hematol., 27, 742–750.

  • Moreau N, Aumais JP, Prudhomme C, Morris SM and Yu-Lee L-Y . (2001). Intl. J. Dev. Biol., 45, 839–843.

  • Morris NR . (2000). J. Cell Biol., 148, 1097–1101.

  • Morris SM, Albrecht U, Reiner O, Eichele G and Yu-Lee L-Y . (1998). Curr. Biol., 8, 603–606.

  • Morris SM, Anaya P, Xiang X, Morris NR, May GS and Yu-Lee L-Y . (1997). Mol. Endocrinol., 11, 229–236.

  • Morris SM and Yu-Lee L-Y . (1998). Exp. Cell Res., 238, 23–32.

  • Niethammer M, Smith DS, Ayala R, Peng J, Ko J, Lee M-S, Morabito M and Tsai L-H . (2000). Neuron., 28, 697–711.

  • Nigg EA . (2001). Nat. Rev. Mol. Cell Biol., 2, 21–32.

  • Nigg EA . (2002). Nat. Rev. Cancer, 2, 1–11.

  • Osmani AH, Osmani SA and Morris NR . (1990). J. Cell Biol., 111, 543–551.

  • Peterson JR and Mitchison TJ . (2002). Chem. Biol., 9, 1275–1285.

  • Quintyne NJ, Gill SR, Eckley DM, Crego CL, Compton DA and Schroer TA . (1999). J. Cell Biol., 147, 321–334.

  • Quintyne NJ and Schroer TA . (2002). J. Cell Biol., 159, 245–254.

  • Rockwell SC, Kallman RF and Fajardo LF . (1972). J. Natl. Cancer Inst., 49, 735–749.

  • Rowinsky EK and Donehower RC . (1995). New Engl. J. Med., 332, 1004–1014.

  • Salina D, Bodoor K, Eckley DM, Schroer TA, Rattner JB and Burke B . (2002). Cell, 108, 97–107.

  • Smith DS, Niethammer M, Ayala R, Zhou Y, Gambello MJ, Wynshaw-Boris A and Tsai L-H . (2000). Nat. Cell Biol., 2, 767–775.

  • Stone KR, Mickey DD, Wunderli H, Mickey GH and Paulson DF . (1978). Int. J. Cancer, 21, 274–281.

  • Straight AF and Field CM . (2000). Curr. Biol., 10, R760–R770.

  • Tai C-Y, Dujardin DL, Faulkner NE and Vallee RB . (2002). J. Cell Biol., 156, 959–968.

  • Talcott B and Moore MS . (2000). J. Biol. Chem., 275, 10099–10104.

  • Wood KW, Cornwell WD and Jackson JR . (2001). Curr. Op. Pharmacol., 1, 370–377.

  • Yan X, Li F, Liang Y, Shen Y, Zhao X, Huang Q and Zhu X . (2003). Mol. Biol. Cell, 23, 1239–1250.

  • Zhang M-Y, Huang N-N, Clawson GA, Osmani SA, Pan W, Xin P, Razzaque MS and Miller BA . (2002). Exp. Cell Res., 273, 73–84.

  • Zhou T, Aumais JP, Liu X, Yu-Lee L-y and Erikson RL . (2003). Dev. Cell, 5, 127–138.

Download references

Acknowledgements

We thank Dr Mary Moore and Alice Su for help with the MetaMorph software program. This work was supported by a McNair Fellowship to MN, funding from the Linda and Ronald Finger Lupus Research Center to L-yY-L, and grants from the National Institutes of Health (RO1 CA86342) to S-HL and (RO1 DK53176) to L-yY-L.

Author information

Authors and Affiliations

  1. Department of Molecular Pathology, MD Anderson Cancer Center, Houston, TX, USA

    Sue-Hwa Lin, Weiping Luo & Matthew Galfione

  2. Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX, USA

    Michiya Nishino & Li-yuan Yu-Lee

  3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    Jonathan P Aumais & Li-yuan Yu-Lee

  4. Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, Texas

    Jian Kuang

  5. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Li-yuan Yu-Lee

Authors
  1. Sue-Hwa Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michiya Nishino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weiping Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonathan P Aumais
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew Galfione
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Kuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li-yuan Yu-Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li-yuan Yu-Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, SH., Nishino, M., Luo, W. et al. Inhibition of prostate tumor growth by overexpression of NudC, a microtubule motor-associated protein. Oncogene 23, 2499–2506 (2004). https://doi.org/10.1038/sj.onc.1207343

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207343

Keywords

This article is cited by

Search

Advanced search

Quick links