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A role for BRCA1 in sporadic breast cancer.

Fraser JA, Reeves JR, Stanton PD, Black DM, Going JJ, Cooke TG, Bartlett JM - Br. J. Cancer (2003)

Bottom Line: Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006).BRCA1 protein is postulated to function as a tumour suppressor.BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

View Article: PubMed Central - PubMed

Affiliation: University Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
To test the hypothesis that altered expression of BRCA1 protein may play an important role in sporadic breast cancer development, 50 randomly selected primary breast cancers (frozen sections, 5 years' median follow-up) were immunolabelled with two monoclonal BRCA1 antibodies (MS110 and MS13). MS110 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecificity. MS13 labelling was predominantly cytoplasmic. Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006). Western blotting detected a 110 kDa molecule consistent with BRCA1 delta11b splice variant. BRCA1 protein is postulated to function as a tumour suppressor. We demonstrate cytoplasmic localisation in sporadic breast cancer suggesting excess delta11b splice variant production, reduced production of full-length BRCA1 and thus postulate reduced tumour suppressor activity. BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

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Related in: MedlinePlus

Sporadic breast cancer tumours (tumour A lanes 1 and 2, tumour B lanes 3 and 4). Whole-cell protein lysate (100 and 200 μg aliquots) probed with MS13 demonstrating the presence of one detected molecule of 110 kDa.
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fig5: Sporadic breast cancer tumours (tumour A lanes 1 and 2, tumour B lanes 3 and 4). Whole-cell protein lysate (100 and 200 μg aliquots) probed with MS13 demonstrating the presence of one detected molecule of 110 kDa.

Mentions: Low- and high-scoring tumours from the MS13 immunostained group were selected and protein was extracted for Western blotting. This confirmed MS13 to label a 110 kDa molecule in the tumour setting, consistent with the cell line Western blot findings (Figure 5Figure 5


A role for BRCA1 in sporadic breast cancer.

Fraser JA, Reeves JR, Stanton PD, Black DM, Going JJ, Cooke TG, Bartlett JM - Br. J. Cancer (2003)

Sporadic breast cancer tumours (tumour A lanes 1 and 2, tumour B lanes 3 and 4). Whole-cell protein lysate (100 and 200 μg aliquots) probed with MS13 demonstrating the presence of one detected molecule of 110 kDa.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747570&req=5

fig5: Sporadic breast cancer tumours (tumour A lanes 1 and 2, tumour B lanes 3 and 4). Whole-cell protein lysate (100 and 200 μg aliquots) probed with MS13 demonstrating the presence of one detected molecule of 110 kDa.
Mentions: Low- and high-scoring tumours from the MS13 immunostained group were selected and protein was extracted for Western blotting. This confirmed MS13 to label a 110 kDa molecule in the tumour setting, consistent with the cell line Western blot findings (Figure 5Figure 5

Bottom Line: Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006).BRCA1 protein is postulated to function as a tumour suppressor.BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

View Article: PubMed Central - PubMed

Affiliation: University Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.

ABSTRACT
To test the hypothesis that altered expression of BRCA1 protein may play an important role in sporadic breast cancer development, 50 randomly selected primary breast cancers (frozen sections, 5 years' median follow-up) were immunolabelled with two monoclonal BRCA1 antibodies (MS110 and MS13). MS110 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecificity. MS13 labelling was predominantly cytoplasmic. Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006). Western blotting detected a 110 kDa molecule consistent with BRCA1 delta11b splice variant. BRCA1 protein is postulated to function as a tumour suppressor. We demonstrate cytoplasmic localisation in sporadic breast cancer suggesting excess delta11b splice variant production, reduced production of full-length BRCA1 and thus postulate reduced tumour suppressor activity. BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

Show MeSH
Related in: MedlinePlus