Modulation of Bcl-2 and Ki-67 expression in oestrogen receptor-positive human breast cancer by tamoxifen.
The expression of the bcl-2 proto-oncogene, which is associated with prolonged cell survival and prevention of programmed cell death, was investigated in human primary breast carcinomas prior to and following endocrine therapy with the anti-oestrogen, tamoxifen. Using the BCL-2-100 antibody, a 26-kD protein was detected by western immunoblot in the cytosols of oestrogen receptor (ER)+ve human breast cancers. In a cross-sectional study, the immunohistochemical expression of Bcl-2 was observed in 32% of invasive breast cancers, but in 65% of tumours treated with tamoxifen (P = 0.009). There was a significant association of Bcl-2 with ER status, with 64% of untreated and 88% of tamoxifen-treated Bcl-2-positive tumours being ER+ve. A significantly lower Ki-67 score was found in tamoxifen-treated tumours which were Bcl-2-positive compared with Bcl-2-negative (9.3 versus 24.6%, P = 0.01). In a separate series of sequential Trucut biopsies from 18 patients, the frequency of Bcl-2 expression was increased in ER+ve tumours from 3/12 to 8/11 following tamoxifen (P = 0.04). This was also associated with a significant reduction in mean Ki-67 score from 32 to 12% (P = 0.0004). The observations from this study clearly indicate that Bcl-2 in human breast cancer is associated with ER status, and that expression is enhanced in ER+ve tumours following tamoxifen, in association with reduced cell proliferation.
Department of Biochemistry, Royal Marsden Hospital, London, U.K.
S R
SR
Johnston
K A
KA
MacLennan
N P
NP
Sacks
J
J
Salter
I E
IE
Smith
M
M
Dowsett
D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019394:Ki-67 Antigen; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*
D019394:Ki-67 Antigen; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D013629:Tamoxifen