Inhibition of prostate tumor growth by overexpression of NudC, a microtubule motor-associated protein.
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.
Lin
Sue-Hwa
SH
Department of Molecular Pathology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Nishino
Michiya
M
Luo
Weiping
W
Aumais
Jonathan P
JP
Galfione
Matthew
M
Kuang
Jian
J
Yu-Lee
Li-Yuan
LY
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D002455:Cell Division; D045744:Cell Line, Tumor; D048429:Cell Size; D004247:DNA / Q000032:analysis; D004398:Dyneins / Q000378:metabolism; D016195:G2 Phase; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000628:therapy*; D011506:Proteins / Q000378:metabolism* / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000378:metabolism; D014183:Transplantation, Heterologous
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C512648:NUDC protein, human; D009687:Nuclear Proteins; C512649:Nudc protein, mouse; D011506:Proteins; D011994:Recombinant Proteins; D004247:DNA; D004398:Dyneins