Significance of nuclear hTra2-beta1 expression in cervical cancer.
OBJECTIVE
Human Tra2-beta1, a member of the serine/arginine-rich splicing factors, is involved in C/A-dependent mRNA processing and regulation of gene expression. Since several genes involved in cervical carcinogenesis are alternatively spliced and contain C/A rich elements, we aimed to analyze hTra2-beta1 expression and subcellular localization in tumor tissue of women with cervical cancer and to determine its clinical significance.


METHODS
Retrospective study.


METHODS
Tertiary-care academic medical center.


METHODS
One hundred and five patients with cervical cancer and a mean follow up time of 73.1 months.


METHODS
Immunohistochemistry of paraffin-embedded tissues was performed and hTra2-beta1 expression was correlated with clinico-pathological variables including patient outcome.


RESULTS
Cytoplasmic hTra2-beta1 protein expression was found in 20% of cases, while all tumors revealed nuclear immunoreactivity with strong expression in 54.3% of cases. There was a significant inverse correlation between nuclear and cytoplasmic protein expression, suggesting a potentially relevant shuttle process of hTra2-beta1 between both cellular compartments. Patients with weak expressing hTra2-beta1 tumors showed an improved survival with a tumor-related death rate of 8.3% compared to 23.7% in patients with moderate and high intranuclear hTra2-beta1 expression, respectively.


CONCLUSIONS
Our data support the hypothesis of a biological relevance for hTra2-beta1 expression in cervical cancer. The observed shuttle process of this splicing factor with higher concentrations in the nucleus should have pronounced effects on the cellular function and tumor biology of the affected tumors, leading to the worse patient outcome.
Gabriel
Boris
B
Department of Obstetrics and Gynecology, Freiburg University Medical Center, Freiburg, Germany.
Zur Hausen
Axel
A
Bouda
Jiri
J
Boudova
Ludmila
L
Koprivova
Miroslava
M
Hirschfeld
Marc
M
Jager
Markus
M
Stickeler
Elmar
E
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D016601:RNA-Binding Proteins / Q000032:analysis*; D000068103:Serine-Arginine Splicing Factors; D016019:Survival Analysis; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C097083:TRA2B protein, human; D000068103:Serine-Arginine Splicing Factors