TY - JOUR
T1 - Estradiol stabilizes p53 protein in breast cancer cell line, MCF-7
AU - Okumura, Naoki
AU - Saji, Shigehira
AU - Eguchi, Hidetaka
AU - Hayashi, Shin Ichi
AU - Saji, Shigetoyo
AU - Nakashima, Shigeru
PY - 2002/8
Y1 - 2002/8
N2 - Overexpression of the oncoprotein MDM2, an important regulator of the p53 tumor suppressor protein, is often observed in breast cancer tissues and cell lines, particularly in those which express estrogen receptor α (ERα). In MCF-7 breast cancer cell line possessing wild-type p53, ERα and overexpressing MDM2, p53 accumulation was stimulated by 17β-estradiol (E2) in a concentration-dependent manner. On the other hand, E2 caused no change of the expression of p53 mRNA, indicating that E2 affects p53 at the post-transcriptional level. To analyze the mechanism of p53 accumulation by E2, the stability of p53, ERα and MDM2 proteins was analyzed in the presence of cycloheximide under an E2-supplemented or -depleted condition. E2 significantly extended the half-life of p53 protein, but shortened that of ERα in MCF-7 cells. E2 significantly decreased the stability of p90(MDM2) and p60(MDM2) in MCF-7. Interestingly, E2 increased the ratio p60(MDM2)/p9O(MDM2) inversely proportionally to the degradation of p53. These results suggest that the ratio of the two MDM2 proteins, p90(MDM2) and p60(MDM2), may affect the accumulation of wild-type p53 protein in response to E2.
AB - Overexpression of the oncoprotein MDM2, an important regulator of the p53 tumor suppressor protein, is often observed in breast cancer tissues and cell lines, particularly in those which express estrogen receptor α (ERα). In MCF-7 breast cancer cell line possessing wild-type p53, ERα and overexpressing MDM2, p53 accumulation was stimulated by 17β-estradiol (E2) in a concentration-dependent manner. On the other hand, E2 caused no change of the expression of p53 mRNA, indicating that E2 affects p53 at the post-transcriptional level. To analyze the mechanism of p53 accumulation by E2, the stability of p53, ERα and MDM2 proteins was analyzed in the presence of cycloheximide under an E2-supplemented or -depleted condition. E2 significantly extended the half-life of p53 protein, but shortened that of ERα in MCF-7 cells. E2 significantly decreased the stability of p90(MDM2) and p60(MDM2) in MCF-7. Interestingly, E2 increased the ratio p60(MDM2)/p9O(MDM2) inversely proportionally to the degradation of p53. These results suggest that the ratio of the two MDM2 proteins, p90(MDM2) and p60(MDM2), may affect the accumulation of wild-type p53 protein in response to E2.
KW - Breast cancer
KW - Estrogen receptor
KW - MDM2
KW - P53
UR - http://www.scopus.com/inward/record.url?scp=0036671883&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036671883&partnerID=8YFLogxK
U2 - 10.1111/j.1349-7006.2002.tb01331.x
DO - 10.1111/j.1349-7006.2002.tb01331.x
M3 - Article
C2 - 12716463
AN - SCOPUS:0036671883
VL - 93
SP - 867
EP - 873
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 8
ER -