Adenovirus-mediated gene transfer to human breast tumor cells: An approach for cancer gene therapy and bone marrow purging

Prem Seth, Ulrich Brinkmann, Gretchen N. Schwartz, Dai Katayose, Ronald Gress, Ira Pastan, Kenneth Cowan

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

To examine the potential use of adenovirus vectors in cancer gene therapy as a mechanism for purging bone marrow cells of possible breast cancer contaminants, we compared the infection efficiency of adenovirus and the transfection efficiency of plasmid DNA in the presence of adenovirus in human breast cancer and bone marrow cells. Following infection of breast cancer cells with an adenovirus expressing β-galactosidase gene, high levels of β- galactosidase activity were observed. No β-galactosidase activity was observed in low-density human bone marrow cells. A replication-deficient adenovirus mutant d1312 enhanced the transfection efficiency of a plasmid DNA-expressing β-galactosidase gene into breast cancer cells, and addition of a liposome, lipofectamine, further enhanced the transfection efficiency. In contrast, human bone marrow cells treated under the same conditions expressed very low levels of the transfected β-galactosidase DNA. Transfection of cells with plasmid DNA expressing a truncated but fully active Pseudomonas exotoxin gene in the presence of d1312 and lipofectamine resulted in marked breast cancer cell killing, whereas colony-forming unit granulocyte-macrophage (CFU-GM) were relatively resistant to these treatments. A recombinant adenovirus expressing human wild-type p53 protein (AdWTp53) was also highly cytotoxic to breast tumor cells. Infection of breast cancer cells with AdWTp53 (100 plaque-forming units/cell) resulted in 100% loss of the clonogenicity of breast tumor cells. However, colony formation from CFU-GM was relatively resistant to the cytotoxic effects of AdWTp53 alone or in the presence of pULI100 plasmid and lipofectamine. On the basis of these results, it is proposed that human adenoviruses are potentially useful for cancer gene therapy and bone marrow purging.

Original languageEnglish (US)
Pages (from-to)1346-1351
Number of pages6
JournalCancer Research
Volume56
Issue number6
StatePublished - Mar 15 1996

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Bone Marrow Purging
Bone Neoplasms
Neoplasm Genes
Adenoviridae
Genetic Therapy
Galactosidases
Breast Neoplasms
Human Adenoviruses
Bone Marrow Cells
Genes
Transfection
Plasmids
Granulocyte-Macrophage Progenitor Cells
DNA
Adenoviridae Infections
Exotoxins
Pseudomonas
Infection
Liposomes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Seth, P., Brinkmann, U., Schwartz, G. N., Katayose, D., Gress, R., Pastan, I., & Cowan, K. (1996). Adenovirus-mediated gene transfer to human breast tumor cells: An approach for cancer gene therapy and bone marrow purging. Cancer Research, 56(6), 1346-1351.

Adenovirus-mediated gene transfer to human breast tumor cells : An approach for cancer gene therapy and bone marrow purging. / Seth, Prem; Brinkmann, Ulrich; Schwartz, Gretchen N.; Katayose, Dai; Gress, Ronald; Pastan, Ira; Cowan, Kenneth.

In: Cancer Research, Vol. 56, No. 6, 15.03.1996, p. 1346-1351.

Research output: Contribution to journalArticle

Seth, P, Brinkmann, U, Schwartz, GN, Katayose, D, Gress, R, Pastan, I & Cowan, K 1996, 'Adenovirus-mediated gene transfer to human breast tumor cells: An approach for cancer gene therapy and bone marrow purging', Cancer Research, vol. 56, no. 6, pp. 1346-1351.
Seth P, Brinkmann U, Schwartz GN, Katayose D, Gress R, Pastan I et al. Adenovirus-mediated gene transfer to human breast tumor cells: An approach for cancer gene therapy and bone marrow purging. Cancer Research. 1996 Mar 15;56(6):1346-1351.
Seth, Prem ; Brinkmann, Ulrich ; Schwartz, Gretchen N. ; Katayose, Dai ; Gress, Ronald ; Pastan, Ira ; Cowan, Kenneth. / Adenovirus-mediated gene transfer to human breast tumor cells : An approach for cancer gene therapy and bone marrow purging. In: Cancer Research. 1996 ; Vol. 56, No. 6. pp. 1346-1351.
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