BRCA1 5083del19 mutant allele selectively up-regulates periostin expression in vitro and in vivo.
OBJECTIVE
The aim of this study was to explore the gene expression pattern produced by the cancer-associated BRCA1 5083del19 founder mutation by using a microarray analysis. Such a mutation, identified in a subset of familial breast cancer patients, involves a deletion at the 3' end of the BRCA1 messenger leading, in the mature protein, to the ablation of the BRCT tandem domain.


METHODS
We generated HeLa cells stably expressing both exogenous wild-type (HeLa/(wt)BRCA1), used as a control, and 5083del19 BRCA1 (HeLa/(5083del19)BRCA1) alleles; gene chips were then used to investigate any changes in the transcription profile induced by the 5083del19 BRCA1 mutant compared with controls.


RESULTS
Among the genes showing perturbation of their expression, periostin was found to be up-regulated in HeLa/(5083del19)BRCA1 cells to an extent of 72-fold versus HeLa/(pcDNA3.1/empty) and 76-fold versus HeLa/(wt)BRCA1 cells. This finding was validated both in vitro in breast cancer cell lines harboring mutations of BRCA1 and in vivo by immunohistochemistry of breast cancer specimens bearing the 5083del19 BRCA1 mutation as well as by Western blot analysis of sera obtained from patients and healthy carriers of the same mutation.


CONCLUSIONS
Our results suggest that periostin overexpression, whose product is released from cells in the extracellular fluids, might be a potential marker for early cancer detection in a specific subset of hereditary breast carcinomas triggered by cancer-associated BRCA1 mutations that affect the BRCT tandem domain.
Quaresima
Barbara
B
Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy.
Romeo
Francesco
F
Faniello
Maria C
MC
Di Sanzo
Maddalena
M
Liu
Chang-Gong
CG
Lavecchia
Annamaria
A
Taccioli
Cristian
C
Gaudio
Eugenio
E
Baudi
Francesco
F
Trapasso
Francesco
F
Croce
Carlo M
CM
Cuda
Giovanni
G
Costanzo
Francesco
F
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D018703:Founder Effect; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; C512835:POSTN protein, human