Nuclear localisation of LASP-1 correlates with poor long-term survival in female breast cancer.
BACKGROUND
LIM and SH3 protein 1 (LASP-1) is a nucleo-cytoplasmatic signalling protein involved in cell proliferation and migration and is upregulated in breast cancer in vitro studies have shown that LASP-1 might be regulated by prostate-derived ETS factor (PDEF), p53 and/or LASP1 gene amplification. This current study analysed the prognostic significance of LASP-1 on overall survival (OS) in 177 breast cancer patients and addressed the suggested mechanisms of LASP-1-regulation.


METHODS
Nucleo-cytoplasmatic LASP-1-positivity of breast carcinoma samples was correlated with long-term survival, clinicopathological parameters, Ki67-positivity and PDEF expression. Rate of LASP1 amplification was determined in micro-dissected primary breast cancer cells using quantitative RT-PCR. Cell-phase dependency of nuclear LASP-1-localisation was studied in synchronised cells. In addition, LASP-1, PDEF and p53 expression was compared in cell lines of different tumour entities to define principles for LASP-1-regulation.


RESULTS
We showed that LASP-1 overexpression is not due to LASP1 gene amplification. Moreover, no correlation between p53-mutations or PDEF-expression and LASP-1-status was observed. However, nuclear LASP-1-localisation in breast carcinomas is increased during proliferation with peak in G2/M-phase and correlated significantly with Ki67-positivity and poor OS.


CONCLUSIONS
Our results provide evidence that nuclear LASP-1-positivity may serve as a negative prognostic indicator for long-term survival of breast cancer patients.
Frietsch
J J
JJ
Institute for Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Grombuehlstr. 12, 97080 Wuerzburg, Germany.
Grunewald
T G P
TG
Jasper
S
S
Kammerer
U
U
Herterich
S
S
Kapp
M
M
Honig
A
A
Butt
E
E
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification / Q000502:physiology; D006801:Humans; D060588:LIM Domain Proteins; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D017741:Survivors / Q000706:statistics & numerical data; D013997:Time Factors; D014018:Tissue Distribution
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins
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