Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines

Abstract

Lactoferrin (LF), traditionally known as an iron-binding protein present in high concentrations in milk and various secretions, has emerged as a multifunctional protein involved in many aspects of the host defense against infection. Recently, LF has been shown to inhibit the growth of solid tumors and reduce experimental metastasis in mice, suggesting that LF also may play a role in the defense against tumorigenesis. Here we provide the sequence of the cDNA and promoter region, the chromosome assignment, and tissue expression pattern of a novel form of LF mRNA (ΔLF). The sequence of ΔLF mRNA is nearly identical to that of LF mRNA; however, at the 5' end, we find a novel sequence that replaces the N-terminal signal peptide sequence of LF mRNA. We map the ΔLF mRNA to human chromosome 3 and find that both ΔLF and LF sequences colocalize to the same cloned 90- to 150-kb genomic DNA fragment. We further show that the ΔLF mRNA is the product of alternative splicing of the LF gene and likely is specified by use of an alternative promoter. Although we find ΔLF mRNA at various levels in 20 of 20 adult and fetal human tissues, we do not find ΔLF mRNA in any of 14 diverse tumor- derived cell lines.