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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

SKOV-3 whole, cytoplasmic and nuclear fractions (100 μg aliquots lanes 1 – 3, and 200 μg aliquots lanes 4–6) probed with (A) MS110 demonstrating multiple bands of various molecular weights and (B) MS13 demonstrating one band of 110 kDa in the whole cell and cytoplasmic fractions and faintly in the nuclear fraction.
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fig4: SKOV-3 whole, cytoplasmic and nuclear fractions (100 μg aliquots lanes 1 – 3, and 200 μg aliquots lanes 4–6) probed with (A) MS110 demonstrating multiple bands of various molecular weights and (B) MS13 demonstrating one band of 110 kDa in the whole cell and cytoplasmic fractions and faintly in the nuclear fraction.

Mentions: MS110 detected both 220 and 110 kDa bands in the whole cell and the nuclear fractions of both cell lines tested as well as numerous other bands, suggesting that, although detecting the full-length and splice variant of BRCA1, MS110 crossreacts with a number of other proteins (Figure 4Figure 4


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)

SKOV-3 whole, cytoplasmic and nuclear fractions (100 μg aliquots lanes 1 – 3, and 200 μg aliquots lanes 4–6) probed with (A) MS110 demonstrating multiple bands of various molecular weights and (B) MS13 demonstrating one band of 110 kDa in the whole cell and cytoplasmic fractions and faintly in the nuclear fraction.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: SKOV-3 whole, cytoplasmic and nuclear fractions (100 μg aliquots lanes 1 – 3, and 200 μg aliquots lanes 4–6) probed with (A) MS110 demonstrating multiple bands of various molecular weights and (B) MS13 demonstrating one band of 110 kDa in the whole cell and cytoplasmic fractions and faintly in the nuclear fraction.
Mentions: MS110 detected both 220 and 110 kDa bands in the whole cell and the nuclear fractions of both cell lines tested as well as numerous other bands, suggesting that, although detecting the full-length and splice variant of BRCA1, MS110 crossreacts with a number of other proteins (Figure 4Figure 4

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