A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females.
BACKGROUND
Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples.


METHODS
32P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue. cDNA probes were hybridized to microarrays and expression levels registered using a phosphorimager. Expression levels of some genes were validated by real time RT-PCR and immunohistochemical assays.


RESULTS
We identified two subgroups of tumors according to their expression profiles, probably related with cancer progression. Ten genes, unexpressed in normal tissue, were turned on in some tumors. We found consistent high expression of Bik gene in 14/15 tumors with predominant cytoplasmic distribution.


CONCLUSIONS
Recently, the product of the Bik gene has been associated with tumoral reversion in different neoplasic cell lines, and was proposed as therapy to induce apoptosis in cancers, including breast tumors. Even though a relationship among genes, for example those from a particular pathway, can be observed through microarrays, this relationship might not be sufficient to assign a definitive role to Bik in development and progression of the neoplasia. The findings herein reported deserve further investigation.
García
Normand
N
Molecular Genetics Laboratory, Pediatric Hospital, National Medical Center Century XXI, Mexican Social Security Institute, Mexico City, Mexico. normandgarcia@yahoo.com
Salamanca
Fabio
F
Astudillo-de la Vega
Horacio
H
Curiel-Quesada
Everardo
E
Alvarado
Isabel
I
Peñaloza
Rosenda
R
Arenas
Diego
D
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis*; D008800:Mexico; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger