WWOX--the FRA16D cancer gene: expression correlation with breast cancer progression and prognosis.
OBJECTIVE
WWOX is a tumour suppressor gene involved in various tumours including breast cancer. High chromosomal abnormalities in a genomic region spanned by WWOX are associated with the fact that this gene covers approximately 1 million base pairs of the second most affected among common chromosomal fragile sites FRA16D. We evaluated WWOX expression levels in breast cancer samples in association with diagnostics-prognostics markers.


METHODS
We performed quantitative real-time RT-PCR to analyse levels of expression of WWOX in 132 cases of breast cancer. We evaluated the relationship between WWOX mRNA levels, clinico-pathological factors, expression of aberrant WWOXDelta6-8 mRNA and other cancer related genes.


RESULTS
Expression of WWOX was higher in patients younger than 50 years old, in ER and PR positive tumours vs negative for those receptors and tumours without lymph node metastasis vs LN+. WWOX mRNA levels were also higher in tumours with higher apoptotic index (Bcl2/Bax ratio). Negative associations were found between WWOX expression and cytokeratins 5/6 and 17 (P<0.05). High level expression of WWOX was also associated with better disease free survival. Presence of WWOXDelta6-8 transcripts were accompanied with lower WWOX wild type mRNA level.


CONCLUSIONS
Reduced WWOX expression commonly observed in various neoplasias in cases of breast cancer is associated with markers of bad prognosis. Our findings reveal additional evidence that WWOX may be involved in steroid (estrogens) metabolism and signaling pathways. WWOX can be considered as a new target for gene therapy development due to the association of high WWOX expression with improved disease free survival.
Płuciennik
E
E
Department of Molecular Cancerogenesis, Medical University of Lodz, Mazowiecka St 6/8, 92-215 Lodz, Poland.
Kusińska
R
R
Potemski
P
P
Kubiak
R
R
Kordek
R
R
Bednarek
A K
AK
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D011044:Poland; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human