Nuclear localization and cytosolic overexpression of LASP-1 correlates with tumor size and nodal-positivity of human breast carcinoma.
BACKGROUND
LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration, which was reported to be overexpressed in 8-12 % of human breast cancers and thought to be exclusively located in cytoplasm.


METHODS
In the present work we analyzed the cellular and histological expression pattern of LASP-1 and its involvement in biological behavior of human breast cancer through correlation with standard clinicopathological parameters and expression of c-erbB2 (HER-2/neu), estrogen- (ER) and progesterone-receptors (PR). For this purpose immunohistochemical staining intensity and percentage of stained cells were semi-quantitatively rated to define a LASP-1 immunoreactive score (LASP-1-IRS). LASP-1-IRS was determined in 83 cases of invasive ductal breast carcinomas, 25 ductal carcinomas in situ (DCIS) and 18 fibroadenomas. Cellular LASP-1 distribution and expression pattern was visualized by immunofluorescence and confocal microscopy and assessed through separate Western blots of nuclear and cytosol preparations of BT-20, MCF-7, MDA-MB231, and ZR-75/1 breast cancer cells.


RESULTS
Statistical analysis revealed that the resulting LASP-1-IRS was significantly higher in invasive carcinomas compared to fibroadenomas (p = 0.0176). Strong cytoplasmatic expression of LASP-1 was detected in 55.4 % of the invasive carcinomas, which correlated significantly with nuclear LASP-1-positivity (p = 0.0014), increased tumor size (p = 0.0159) and rate of nodal-positivity (p = 0.0066). However, levels of LASP-1 expression did not correlate with average age at time point of diagnosis, histological tumor grading, c-erbB2-, ER- or PR-expression. Increased nuclear localization and cytosolic expression of LASP-1 was found in breast cancer with higher tumor stage as well as in rapidly proliferating epidermal basal cells. Confocal microscopy and separate Western blots of cytosolic and nuclear preparations confirmed nuclear localization of LASP-1.


CONCLUSIONS
The current data provide evidence that LASP-1 is not exclusively a cytosolic protein, but is also detectable within the nucleus. Increased expression of LASP-1 in vivo is present in breast carcinomas with higher tumor stage and therefore may be related with worse prognosis concerning patients' overall survival.
Grunewald
Thomas G P
TG
Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Grombuehlstr, 12, D-97080 Wuerzburg, Germany. Thgruenewald@web.de
Kammerer
Ulrike
U
Kapp
Michaela
M
Eck
Matthias
M
Dietl
Johannes
J
Butt
Elke
E
Honig
Arnd
A
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060588:LIM Domain Proteins; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D017434:Protein Structure, Tertiary
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins