title: Elevated expression and altered processing of fibulin-1 protein in human breast cancer.
abstract: The extracellular matrix protein fibulin-1 suppresses the motility and invasiveness of a variety of tumour cell types in vitro as well as the growth of fibrosarcoma tumours in nude mice. In this study, fibulin-1 protein expression in breast carcinoma specimens and normal breast tissue was evaluated immunohistologically. Fibulin-1 protein expression was also semiquantitatively assessed by immunoblot analysis in a collection of normal breast tissues (n=18), benign tumours (n=5) and breast carcinomas (n=39). In normal breast tissue, fibulin-1 protein expression predominated in the ductal epithelium and underlying myoepithelium, with weaker staining evident in the loose connective surrounding the ducts. Examination of breast carcinomas revealed that the tumour cells also expressed fibulin-1 protein. The level of mature fibulin-1 polypeptide (100 kDa) was higher in the breast carcinoma specimens as compared to normal breast tissue (Mann-Whitney U-test, P=0.0005). In addition to the mature fibulin-1 polypeptide, several smaller sized polypeptides of 55, 50 and 25 kDa were detected using monoclonal antibodies reactive towards an epitope located at the N-terminus of fibulin-1. The immunoreactive 50 kDa polypeptide was detected more frequently in breast carcinoma specimens than in normal breast tissue (chi(2)=17.22, P<0.0001). Furthermore, the ratio of the 50 kDa fragment to the mature fibulin-1 polypeptide correlated with the level of oestrogen receptor alpha (Spearman correlation coefficient, rs=0.49, P<0.003, n=36) and progesterone receptor (rs=0.43, P=0.008, n=36) expression in the tumour specimens. Taken together, these findings indicate that elevated expression and altered processing of fibulin-1 is associated with human breast cancer.
authors.affiliation: Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Ireland.
authors.forename: L M
authors.initials: LM
authors.lastname: Greene
authors.forename: W O
authors.initials: WO
authors.lastname: Twal
authors.forename: M J
authors.initials: MJ
authors.lastname: Duffy
authors.forename: E W
authors.initials: EW
authors.lastname: McDermott
authors.forename: A D
authors.initials: AD
authors.lastname: Hill
authors.forename: N J
authors.initials: NJ
authors.lastname: O'Higgins
authors.forename: A H
authors.initials: AH
authors.lastname: McCann
authors.forename: P A
authors.initials: PA
authors.lastname: Dervan
authors.forename: W S
authors.initials: WS
authors.lastname: Argraves
authors.forename: W M
authors.initials: WM
authors.lastname: Gallagher
mesh_terms: D000911:Antibodies, Monoclonal; D001940:Breast / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011960:Receptors, Estrogen / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D011960:Receptors, Estrogen; C060820:fibulin