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

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.

Incrimination of Heterogeneous Nuclear Ribonucleoprotein E1 (hnRNP-E1) as a Candidate Sensor of Physiological Folate Deficiency

“…Cell Culture-Folate-replete HeLa-IU 1 -HF cells and folatedeficient HeLa-IU 1 -LF cells were obtained (25) and propagated as described (24). Briefly, HeLa-IU 1 -HF cells were propagated long term at 37°C in 5% CO 2 in high folate minimum essential medium (MEM-HF) (Invitrogen) containing 10% nondialyzed fetal bovine serum and 9 nM 5-methyltetrahydrofolate plus 2.3 M pteroylglutamate.…”

“…3A, lane 1), which accounts for the base-line biosynthesis rate of FR (Fig. 3C) and abundant cell surface FR expression (24,25). Indeed, Fig.…”

Translational upregulation of folate receptors is mediated by homocysteine via RNA-heterogeneous nuclear ribonucleoprotein E1 interactions

“…2). The native membrane-associated FR glycoprotein of cervical cancer (HeLa-IU 1 ) cells is hydrophobic and binds a significant amount of Triton X-100 detergent upon solubilization (3). This hydrophobicity is conferred primarily by its glycosylphosphatidylinositol (GPI)-anchored tail, which can be cleaved off by GPI-specific phospholipase C and/or D to give rise to a hydrophilic species.…”

“…Three days later, cells were exposed to 5 µg/ml of actinomycin D for 2, 4, 6, and 8 hours. Total cellular RNA (10 µg) from unexposed and exposed cells was then analyzed on Northern blots (3).…”

Gene therapy strategies for AIDS-related malignancies

“…ding plasmid that interfered with production of folate receptors retarded cervical cancer tumors both in vitro Summary and perspective and in vivo. 51 Since cervical cancer is so poorly responsive to convenCertain cancers occur with increased frequency in HIVinfected individuals. These are usually incurable, and tional chemotherapy, alternative treatment strategies such as these gene therapies are needed.…”