Open AccessRole of MDM2 Overexpression in Doxorubicin Resistance of Breast Carcinoma
Author(s) -
Suzuki Akio,
Toi Masakazu,
Yamamoto Yutaka,
Saji Shigehira,
Muta Mariko,
Tominaga Takeshi
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00552.x
Subject(s) - doxorubicin , breast carcinoma , cancer research , medicine , mammary gland , mdm2 , carcinoma , breast cancer , oncology , biology , chemotherapy , cancer , genetics , gene
Several oncoproteins or tumor suppressor gene products have been indicated to be of value as predictors of the de novo resistance to cytotoxic agents. In this study, we have investigated the role of MDM2 (murine double minutes) overexpression in doxorubicin resistance of breast cancer. Immunocytochemical analysis demonstrated that MDM2‐positive tumors, even with p53‐negative pheno‐type, were significantly more resistant to doxorubicin treatment compared to MDM2‐negative tumors. An in vitro experimental model using stable mdm2 ‐transfected MCF‐7 cells carrying wild‐type p53 confirmed that the cells become approximately 3‐fold more resistant to doxorubicin as a result of MDM2 overexpression, and the wild‐type p53 function, such as the induction of p21 Waf1 following DNA damage, was significantly suppressed. MDM2 overexpression is suggested to be a novel marker for predicting lack of response to doxorubicin treatment in breast cancer patients.