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

Lin Ji, Masahiko Nishizaki, Boning Gao, David Burbee, Masashi Kondo, Craig Kamibayashi, Kai Xu, Nancy Yen, E. Neely Atkinson, Bingliang Fang, Michael I. Lerman, Jack A. Roth, John D. Minna

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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.

Original languageEnglish
Pages (from-to)2715-2720
Number of pages6
JournalCancer Research
Volume62
Issue number9
Publication statusPublished - 01-05-2002

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Human Chromosomes
Adenoviridae
Gene Expression
Neoplasms
Genes
Lung Neoplasms
Apoptosis
Protamines
Growth
Tumor Suppressor Genes
Heterografts
In Vitro Techniques
Cell Cycle
Protein Isoforms
Epithelial Cells
Cell Proliferation
Breast Neoplasms
Neoplasm Metastasis
Lung
Injections

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ji, Lin ; Nishizaki, Masahiko ; Gao, Boning ; Burbee, David ; Kondo, Masashi ; Kamibayashi, Craig ; Xu, Kai ; Yen, Nancy ; Atkinson, E. Neely ; Fang, Bingliang ; Lerman, Michael I. ; Roth, Jack A. ; Minna, John D. / 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. In: Cancer Research. 2002 ; Vol. 62, No. 9. pp. 2715-2720.
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title = "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",
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.",
author = "Lin Ji and Masahiko Nishizaki and Boning Gao and David Burbee and Masashi Kondo and Craig Kamibayashi and Kai Xu and Nancy Yen and Atkinson, {E. Neely} and Bingliang Fang and Lerman, {Michael I.} and Roth, {Jack A.} and Minna, {John D.}",
year = "2002",
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Ji, L, Nishizaki, M, Gao, B, Burbee, D, Kondo, M, Kamibayashi, C, Xu, K, Yen, N, Atkinson, EN, Fang, B, Lerman, MI, Roth, JA & Minna, JD 2002, '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', Cancer Research, vol. 62, no. 9, pp. 2715-2720.

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. / Ji, Lin; Nishizaki, Masahiko; Gao, Boning; Burbee, David; Kondo, Masashi; Kamibayashi, Craig; Xu, Kai; Yen, Nancy; Atkinson, E. Neely; Fang, Bingliang; Lerman, Michael I.; Roth, Jack A.; Minna, John D.

In: Cancer Research, Vol. 62, No. 9, 01.05.2002, p. 2715-2720.

Research output: Contribution to journalArticle

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T1 - 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

AU - Ji, Lin

AU - Nishizaki, Masahiko

AU - Gao, Boning

AU - Burbee, David

AU - Kondo, Masashi

AU - Kamibayashi, Craig

AU - Xu, Kai

AU - Yen, Nancy

AU - Atkinson, E. Neely

AU - Fang, Bingliang

AU - Lerman, Michael I.

AU - Roth, Jack A.

AU - Minna, John D.

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N2 - 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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