Institute of Medical Oncology, University of Bern, 3010 Bern, Switzerland (DCB)
SERPINB5 was originally described as a breast tumour suppressor, a gene which was active in normal breast epithelial cells and which was down-regulated progressively towards malignancy with increasing degrees of tissue disorder being associated with less frequent instances of expression. Consistent with such a tumour suppressor function, work in vitro and in vivo suggested that maspin suppressed angiogenesis, reduced tumour invasiveness, growth, and metastasis and sensitised cells to apoptosis. It was suggested that maspin exerted these effects, at least in part, through modulation of plasminogen activation. In a breast cancer cell line, the maspin RSL was deemed to be critical for the inhibition of tumour cell invasion and the promotion of cell adhesion to extracellular matrix molecules.
However, recent studies have subsequently painted a more complex and perhaps contradictory picture. Maspin appears to have a critical role in early embryonic development. Homozygous loss of expression in mice knockouts is lethal at the peri-implantation stage. The absence of the protein (-/-) disrupts the formation of the endodermal cell layer whilst maspin heterozygote knockout (+/-) endodermal cells grow more slowly than wild-type (+/+) cells. This is particularly interesting in the context of high-level maspin expression in tumours arising from organs of endodermal origin, such as the GI tract, lungs and thyroid. Furthermore, in LA7 cells, a well characterised rat adenocarcinoma in vitro model of mammary gland differentiation, maspin was shown to negatively regulate dome formation, possibly through the perturbation of cell adhesion. This observation suggests that at least in some situations, maspin expression can block differentiation processes.
The gene is not thought to be a frequent tumour amplification or translocation target.
Jim Heighway ; Shirley Smith ; Naomi Bowers ; Daniel Betticher
SERPINB5 serpin peptidase inhibitor, clade B (ovalbumin), member 5
Atlas Genet Cytogenet Oncol Haematol. 2004-06-01
Online version: http://atlasgeneticsoncology.org/gene/42267/serpinb5