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Expression of several genes in the human chromosome 3p21.3 homozygous deletion region by an adenovirus vector results in tumor suppressor activities in vitro and in vivo

  1. Author:
    Ji, L.
    Nishizaki, M.
    Gao, B. N.
    Burbee, D.
    Kondo, M.
    Kamibayashi, C.
    Xu, K.
    Yen, N.
    Atkinson, E. N.
    Fang, B. L.
    Lerman, M. I.
    Roth, J. A.
    Minna, J. D.

  2. Author Address

    Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Sect Thorac Mol Oncol, Box 445,1515 Holcombe Blvd, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Sect Thorac Mol Oncol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Pharmacol Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA Ji L Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Sect Thorac Mol Oncol, Box 445,1515 Holcombe Blvd, Houston, TX 77030 USA
    1. Year: 2002
  2. Journal: Cancer Research
    1. 62
    2. 9
    3. Pages: 2715-2720
  4. Type of Article: Article
  1. Abstract:

    A group of candidate tumor suppressor genes (designated CACNA2D2, PL6, 101F6, NPRL2, BLU, RASSF1, FUS1, HYAL2, and HYAL1) has been identified in a 120-kb critical tumor homozygous deletion region (found in lung and breast cancers) of human chromosome 3p21.3. We studied the effects of six of these 3p21.3 genes (101F6, NPRL2, BLU, FUS1, HYAL2, and HYAL1) on tumor cell proliferation and apoptosis in human lung cancer cells by recombinant adenovirus-mediated gene transfer in vitro and in vivo. We found that forced expression of wild-type FUS1, 101F6, and NPRL2 genes significantly inhibited tumor cell growth by induction of apoptosis and alteration of cell cycle processes in 3p21.3 120-kb region-deficient (homozygous) H1299 and A549 cells but not in the 3p21.3 120-kb region-heterozygous H358 and the normal human bronchial epithelial cells. Intratumoral injection of Ad-101F6, Ad-FUS1, Ad-NPRL2, and Ad- HYAL2 vectors or systemic administration of protamine-complexed vectors significantly suppressed growth of H1299 and A549 tumor xenografts and inhibited A549 experimental lung metastases in nu/nu mice. Together, our results, coupled with other studies demonstrating a tumor suppressor role for the RASSSF1A isoform, suggest that multiple contiguous genes in the 3p21.3 120-kb chromosomal region may exhibit tumor suppressor activity in vitro and in vivo.

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