Exon 3 of the α folate receptor gene contains a 5′ splice site which confers enhanced ovarian carcinoma specific expression

Abstract

The human folate receptor (FR) is overexpressed in ovarian carcinoma. FR transcripts are heterogeneous due to the use of two promoters, P1 and P4, and alternative splicing of exon 3. RNase protection assay and RT-PCR revealed higher levels of the transcripts that include exon 3 in lines and specimens from ovarian carcinoma. A P1^chloramphenicol acetyltransferase (CAT) construct containing exon 3 demonstrated efficient reporter expression only in ovarian carcinoma. 5P P and 3P P deleted variants of the P1^CAT construct were analyzed by RT-PCR of the exogenous transcripts and reporter activity. A 5P P splice site and 35 bp downstream intronic region of exon 3 appeared to regulate enhanced FR expression in ovarian carcinoma. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Evaluating cell lines as tumour models by comparison of genomic profiles

“…IGROV1 is often quoted as being of the HGSOC subtype31323334353637383940414243. However, its flat copy-number profile and high mutation frequency place it among the hyper-mutators described above (Figs 1a, 2 and 3).…”

A novel isoform of pro-interleukin-18 expressed in ovarian tumors is resistant to caspase-1 and -4 processing

“…Further studies in transgenic mice, expressing either one IL-15 isoform, showed that only the 48SP-IL-15 is capable to potentiate protective responses against pathogens, while the 21SP-IL15 appeared immune-suppressive (Nishimura et al, 2000). Thus, it is conceivable that during neoplastic transformation alterations of the splicing may favor the production of proteins involved in tumor progression (Galmozzi et al, 2001) or in tumor escape from immune system. The altered capability to produce biologically active forms of IL-15 or of IL-18 may perhaps confer an immune privilege to tumors during neoplastic transformation.…”

Role of folate receptor genes in reproduction and related cancers

“…More recently, FRs have been found to be regulated in a ligand-dependent manner by nuclear receptors; specifically, FR-β expressed in leukemic cells is regulated by retinoic acid receptors (154;155) and FR-α is regulated by steroid receptors (147;156). FR gene regulation occurs by a variety of mechanisms at both transcriptional and post-transcriptional levels (157)(158)(159)(160). Studying FR gene regulation will obviously lead to a better understanding folate physiology.…”