Overexpression of p27 protein in human breast cancer correlates with in vitro resistance to doxorubicin and mitomycin C.
BACKGROUND
The cycle regulatory protein p27, an inhibitor of cyclin-dependent kinase (CDK), has been attributed a role in resistance to cancer chemotherapy. However, the predictive value of p27 for chemosensitivity of breast cancer is still unclear. We therefore analyzed the in vitro chemosensitivity to a series of anticancer agents in fresh breast cancer specimens and correlated it with the respective expression levels of p27.


METHODS
The expression of p27 protein was examined immunohistochemically in 119 patients with primary breast cancer. The in vitro chemosensitivity was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), Doxorubicin (DXR), cisplatin (CDDP) and cyclophosphamide (CPA).


RESULTS
Fifty-six (47%) of the 119 patients demonstrated p27 overexpression. The susceptibility of DXR and MMC in tumors with high p27 expression was significantly higher than that in tumors with low p27 expression.


CONCLUSIONS
Immunohistochemical results regarding p27 might be therapeutically useful as an indicator of response to DXR and/or MMC based adjuvant chemotherapy for breast cancer.
Yang
Q
Q
Department of Surgery, Affiliated Kihoku Hospital. yang-qf@mail.wakavama-med.ac.jp
Sakurai
T
T
Yoshimura
G
G
Takashi
Y
Y
Suzuma
T
T
Tamaki
T
T
Umemura
T
T
Nakamura
Y
Y
Nakamura
M
M
Utsunomiya
H
H
Mori
I
I
Kakudo
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002945:Cisplatin / Q000494:pharmacology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003520:Cyclophosphamide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D016685:Mitomycin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016685:Mitomycin; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil