Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer

Abstract

We investigated the expression levels of human lactoferrin (Lf), a steroid hormone-inducible gene product the expression of which is often altered during oncogenesis, and of ⌬-lactoferrin (⌬Lf), its alternative isoform, which has been shown to be absent from tumor cell lines in commonly used human breast epithelial cell lines, using semiquantitative RT-PCR. Both mRNAs were detected but with levels of expression lower than those found in normal breast epithelial cells. This downregulation was much more visible for ⌬Lf since its expression was either significantly diminished (BT-20, MCF-7 cell lines) or practically absent (MDA-MB-231, T-47D, HBL 100 cell lines). In order to determine whether Lf gene products are useful prognosic tools, we further analyzed their expression levels in 99 primary breast cancer biopsies. ⌬Lf transcripts were found in all of the samples, whereas Lf transcripts were found in 88% of them. Lf and ⌬Lf expression levels were positively correlated (p ‫؍‬ 0.003). Lf expression was related to tumor type with a higher recovery in lobular-type tumors (p ‫؍‬ 0.04). ⌬Lf expression was related to the histoprognostic grading (p ‫؍‬ 0.02). In univariate analyses, ⌬Lf and Lf expressions were prognosis parameters, high concentrations being associated with a longer overall survival.

Use of Wisteria floribunda agglutinin affinity chromatography in the structural analysis of the bovine lactoferrin N-linked glycosylation

“…Furthermore, LF has been shown to have inhibitory effects on tumourigenesis [12,13] and anti-metastatic activity [14][15][16]. LFs contain between 1 and 5 potential glycosylation sites, depending on the species [17][18][19].…”

Immunohistochemical Investigation of Lactoferrin in Human Bone Primary and Metastatic Tumours

“…A variable immunohistochemical expression has been previously elsewhere reported in various human neoplasms, such as carcinomas of the parotid [28], prostate [29], breast [30,31], thyroid [32][33][34], stomach [35], colon-rectum [36], gallbladder [37], astrocytomas and multiforme glioblastomas [38], skin [39], endometrium [40] and kidney [20].…”

La lactoferrine : une protéine multifonctionnelle

“…Des altérations géné-tiques et épigénétiques inactivent le gène de la Lf fournissant aux cellules cancéreuses un réel avantage prolifératif [27]. Il est intéressant de noter que le taux élevé de ces deux transcrits dans des biopsies de glandes mammaires cancéreuses est corrélé à un bon pronostic [28]. Les activités immunomodulatrice, anti-oxydante et anti-tumorale de la Lf suggèrent qu'elle puisse être un candidat très prometteur dans la lutte contre la tumorigenèse ou, en tout cas, dans sa prévention.…”