Expression of BCL-2 in primary breast cancer and its correlation with tumour phenotype. For the International (Ludwig) Breast Cancer Study Group.
BACKGROUND
The role of apoptosis (programmed cell death) in the development and progression of breast cancer is unknown. Recently the bcl-2 gene has been shown to block apoptosis and thus may promote tumour development. BCL-2 is localized to the luminal cells of the normal breast, which are considered to be the origin of malignant breast disease.


METHODS
Immunocytochemistry using anti bcl-2- antibody was performed on 107 breast cancer specimens belonging to node-positive patients from the Ludwig Breast Cancer Studies I-IV and the results were correlated with survival, tumour grade, S-phase, oestrogen and progesterone receptor status and c-erb B-2 expression. Western and Southern blotting together with immunofluorescence were performed on the breast cancer cell lines BT-20, BT-474, MDA-MB-361, T47-D and MCF-7.


RESULTS
In the breast cancer derived cell line MCF-7 BCL-2 is expressed to a level similar to that of the B-lymphoma cell line Karpas 231 with t(14;18)(q32.3;q21.3), but no evidence of a rearrangement or gene amplification was identified. In a study of 107 breast cancers from the International Breast Cancer Study Group Trials I-IV we have demonstrated a very significant inverse correlation of BCL-2 with c-erbB-2 expression (p = 0.002), and a positive correlation with oestrogen receptors (p = 0.001) and progesterone receptors (p = 0.05). In this study there was no correlation of expression with S-phase fraction in the tumours or with any stage in the cell cycle as assessed in MCF-7 cells.


CONCLUSIONS
We conclude that BCL-2 might contribute to the malignant phenotype of breast cancer by modulation of biological behaviour of cancer cells.
Nathan
B
B
Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, London, U.K.
Gusterson
B
B
Jadayel
D
D
O'Hare
M
M
Anbazhagan
R
R
Jayatilake
H
H
Ebbs
S
S
Micklem
K
K
Price
K
K
Gelber
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015139:Blotting, Southern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone