Paralemmin-1 is over-expressed in estrogen-receptor positive breast cancers

Abstract

BackgroundParalemmin-1 is a phosphoprotein lipid-anchored to the cytoplasmic face of membranes where it functions in membrane dynamics, maintenance of cell shape, and process formation. Expression of paralemmin-1 and its major splice variant (Δ exon 8) as well as the extent of posttranslational modifications are tissue- and development-specific. Paralemmin-1 expression in normal breast and breast cancer tissue has not been described previously.ResultsParalemmin-1 mRNA and protein expression was evaluated in ten breast cell lines, 26 primary tumors, and 10 reduction mammoplasty (RM) tissues using real time RT-PCR. Paralemmin-1 splice variants were assessed in tumor and RM tissues using a series of primers and RT-PCR. Paralemmin-1 protein expression was examined in cell lines using Western Blots and in 31 ductal carcinomas in situ, 65 infiltrating ductal carcinomas, and 40 RM tissues using immunohistochemistry. Paralemmin-1 mRNA levels were higher in breast cancers than in RM tissue and estrogen receptor (ER)-positive tumors had higher transcript levels than ER-negative tumors. The Δ exon 8 splice variant was detected more frequently in tumor than in RM tissues. Protein expression was consistent with mRNA results showing higher paralemmin-1 expression in ER-positive tumors.ConclusionsThe differential expression of paralemmin-1 in a subset of breast cancers suggests the existence of variation in membrane dynamics that may be exploited to improve diagnosis or provide a therapeutic target.

Paralemmin-1 is expressed in lymphatic endothelial cells and modulates cell migration, cell maturation and tumor lymphangiogenesis

“…In contrast, paralemmin-1 expression was not detected in BEC of various tissues investigated, indicating that blood endothelia do not express paralemmin-1 or at least at much lower levels than lymphatic endothelia. Previously, paralemmin-1 has been described by immunoperoxidase staining in subpopulations of blood endothelia of rat kidney and adrenal gland, though not brain [24], and of human mammary gland and breast cancers [25]. More comprehensive investigations will be needed to clarify in which types of blood vessels, under which physiological conditions, at which relative levels and by which techniques paralemmin-1 can be detected in BEC.…”

Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar macrophages

“…Paralemmin-3 (PALM3) was first described in Xenopus laevis as Xlgv7/Xlcaax-1 by Cornish et al (13) and belongs to the paralemmins (PALMs) protein family. The PALM protein family includes PALM1, PALM2, PALM3 and palmdelphin (PALMD) (14), and these proteins are highly expressed in the brain, kidney, adrenal gland and mammary gland, as well as in breast cancers (15)(16)(17). Previous studies have implicated PALM1 as having a role in cell shape control, plasma membrane dynamics, cell motility, cancer cell invasiveness and metastatic potential, cell migration and maturation modulation, and tumor lymphangiogenesis (15,16,18).…”

Evolution of the Vertebrate Paralemmin Gene Family: Ancient Origin of Gene Duplicates Suggests Distinct Functions

“…Paralemmin-1 stimulates cell expansion and the extension of filopodia and processes in fibroblasts, and the formation of filopodia, neurites and dendritic spines in neurons [2] , [3] , [4] . Increased expression of paralemmin-1 has been correlated with tumor progression, invasion or metastatic potential [5] , [6] , [7] . Paralemmins associate with lipid rafts and have been proposed to function as adaptors between membrane proteins or with the cortical cytoskeleton [4] .…”