Transduction of folate receptor cDNA into cervical carcinoma cells using recombinant adeno-associated virions delays cell proliferation in vitro and in vivo

Xin Lai Sun, Brian R. Murphy, Qing Jun Li, Sharada Gullapalli, Janet Mackins, Hiremagalur N. Jayaram, Arun Srivastava, Aśok C. Antony

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Although folate receptors (FRs) mediate folate uptake into cells, the independent role of FRs in cell proliferation remains unclear. We tested the hypothesis that transduction of FR cDNA in sense or antisense orientation using recombinant adeno-associated virus modulated FR expression and altered proliferation of cervical carcinoma cells (which constitutively overexpress FR genes). We determined that the integration of recombinant adeno-associated virions was not site specific. When compared with untransduced cells, sense and antisense FR cDNA-transduced cells exhibited an increase and decrease in FR mRNA and FR expression on the cell surface, respectively. However, when compared with antisense FR cDNA-transduced and untransduced cells, sense FR cDNA-transduced cells exhibited statistically significant (a) increases in total FRs, (b) smaller colonies, (c) lowered cell proliferation in vitro, and (d) less tumor volume with dramatic prolongation of tumor doubling times (225.6 h vs. 96 h) after transplantation into nude mice. Finally, (f) using single cell-derived transduced clones, an inverse relationship between cell proliferation and FR expression was established (r = 0.90, P < 0.001). Thus, transduction of sense/antisense FR cDNA into cervical carcinoma cells modulated expression of FRs and had an impact on cell proliferation in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)1535-1547
Number of pages13
JournalJournal of Clinical Investigation
Volume96
Issue number3
DOIs
StatePublished - Sep 1995

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Folic Acid
Virion
Complementary DNA
Cell Proliferation
Carcinoma
In Vitro Techniques
Dependovirus
Tumor Burden
Nude Mice
Clone Cells
Transplantation

Keywords

  • doubling time
  • gene transfer
  • genomic integration
  • transplantation
  • tumor growth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Transduction of folate receptor cDNA into cervical carcinoma cells using recombinant adeno-associated virions delays cell proliferation in vitro and in vivo. / Sun, Xin Lai; Murphy, Brian R.; Li, Qing Jun; Gullapalli, Sharada; Mackins, Janet; Jayaram, Hiremagalur N.; Srivastava, Arun; Antony, Aśok C.

In: Journal of Clinical Investigation, Vol. 96, No. 3, 09.1995, p. 1535-1547.

Research output: Contribution to journalArticle

Sun, Xin Lai ; Murphy, Brian R. ; Li, Qing Jun ; Gullapalli, Sharada ; Mackins, Janet ; Jayaram, Hiremagalur N. ; Srivastava, Arun ; Antony, Aśok C. / Transduction of folate receptor cDNA into cervical carcinoma cells using recombinant adeno-associated virions delays cell proliferation in vitro and in vivo. In: Journal of Clinical Investigation. 1995 ; Vol. 96, No. 3. pp. 1535-1547.
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