Cell lines:
- In a series of breast cancer cell (BCC) lines, an inverse correlation was found between the expression of
Bcl-2 and p53. BT20, Hs578T, MDA-MB-468, and SK-BR-3 BCC expressed high levels of p53 and no
Bcl-2; MDA-MB-436, -157, -361, and MCF-7 BCC expressed
Bcl-2 and very little, if any, p53; finally, BT474, HBL-100, MDA-MB-231 and -435S BCC expressed comparable levels of the two proteins. Overexpression of a mutant p53 in MCF-7 BCC could induce down-regulation of
Bcl-2 both at protein and mRNA level. However, the promoter region of the human
bcl-2 gene does not contain the negative regulatory elementresponsible for the down-regulation (Haldar S. et al., 1994).
Tumors:
- In a study of 283 node-negative breast cancers, a significantly higher fraction of
Bcl-2-positive cells was observed in p53-negative than in p53-positive tumors. The predictive role of
Bcl-2 expression on 6-year relapse-free and overall survival was found to be mainly dependent on p53 expression (Silvestrini R. et al., 1994).
- An inverse correlation between p53 and
Bcl-2 was found in a series of fine-needle aspirates from patients with primary breast carcinoma (Bozzetti C. et al., 1999).
- The long-term prognostic value of tumoural
MDR1 and
MRP-1, along with p53 and other classical parameters, was analysed on 85 node-positive breast cancer patients receiving anthracycline-based adjuvant therapy. All patients underwent tumour resection plus irradiation and adjuvant chemotherapy (the majority receiving fluorouracil-epirubicin-cyclophosphamide). Median follow-up for the 54 alive patients was 7.8 years. Mean age was 53.7 years (range 28-79) and 54 patients were post-menopausal.
MDR1 and
MRP-1 expression were quantified according to an original reverse transcription polymerase chain reaction multiplex assay with colourimetric enzyme-linked immunosorbent assay detection (beta2-microglobulin as control). P53 protein was analysed using an immunoluminometric assay.
MDR1 expression varied within an 11-fold range (mean 94, median 83),
MRP-1 within a 45-fold range (mean 315, median 242) and p53 protein from the limit of detection (0.002 ng mg
-1) up to 35.71 ng mg
-1 (mean 1.18, median 0.13 ng mg
-1). P53 protein was significantly higher in
oestrogen receptor (ER)-negative than in
ER-positive tumours. The higher the p53, the lower the
MDR1 expression. P53 was not linked to
progesterone receptor (PgR) status, S phase fraction, or
MRP-1. Significantly greater
MDR1 expression was observed in grade I tumours. No relationship was observed between
MDR1 and
MRP-1. Neither
MDR1 nor
MRP-1 was linked to
ER or
PgR status. Unlike
MDR1,
MRP-1 was correlated with the S phase: the greater the
MRP-1, the lower the S phase. Univariate Cox analyses revealed that
MDR1,
MRP-1, p53 and S phase had no significant influence on progression-free or specific survival (Ferrero J.M. et al., 2000).
Bozzetti C. et al. (1999)
Bcl-2 expression on fine-needle aspirates from primary breast carcinoma. Cancer 87, 224-230.
Ferrero J.M. et al. (2000) Application of an original RT-PCR-ELISA multiplex assay for
MDR1 and
MRP-1, along with p53 determination in node-positive breast cancer patients. Br. J. Cancer 82, 171-177.
Haldar S. et al. (1994) Down-regulation of
bcl-2 by
p53 in breast cancer cells. Cancer Res. 54, 2095-2097.
Reisman D. et al. (1988) Human p53 oncogene contains one promoter upstream of exon 1 and a second, stronger promoter within intron 1. Proc. Natl. Acad. Sci. USA 85, 5146-5150.
Silvestrini R. et al. (1994) The
Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph-node negative breast cancer patients. J. Natl. Cancer Inst. 86, 499-504.
Vogelstein B. and Kinzler K.W. (1994) X-rays strike p53 again. Nature 370, 174-175.
