Expression of the apoptosis-related genes BCL-2 and BAD in human breast carcinoma and their associated relationship with chemosensitivity.
OBJECTIVE
To evaluate the expression of BCL-2 and BAD genes in tissues of breast carcinoma and investigate the relationship between the expression of BCL-2 and BAD in breast cancer cells with chemosensitivity.


METHODS
Immunohistochemical technique was used to detect the expression of BCL-2, BAD in 10 normal breast tissues, 10 breast fibroadenoma tissues, 40 youth human breast carcinoma tissues, 40 menopause human breast carcinoma tissues. And to detect the expression of ER, PR in 80 human breast carcinoma tissues. 20 Surgical samples of breast cancer, diagnosed by pathology, were obtained from The First Affiliated Hospital of Chongqing Medical University. The cancer sample cells were cultured separately in the incubator at 37 degrees C, 5% CO2 in vitro. The rate of inhibition of cancer cells in 4 kinds of anticancer drugs-- Epirubicin Adriamycin (EADM),5-Fluorouracil (5-Fu), Navelbine(NVB) and Diaminedichloroplatinum (DDP), were assayed by MTT method.


RESULTS
The expression of BCL-2, BAD genes in young human breast carcinoma tissues were lower than that in menopause human breast carcinoma tissues (P < 0.05). There was a negative correlation between the positive expression rate of BCL-2 and histologic grade or the lymph node metastasis (P < 0.05). There was a positive correlation between the expression rates of BCL-2 and of ER, PR (P < 0.05). The expression of BAD had no relationship with the expression of ER, PR, histologic grade and the lymph node metastasis(P = NS). Sensitivity rates of 20 breast cancer cells in 0.1 x PPC within 48 h in vitro were 30% EADM,20% 5-Fu,45% NVB and 25% DDP. Respectively, the rate of inhibition of EADM,5- Fu, NVB and DDP were significantly higher in the BCL-2 negative cancer cells than in the BCL-2 positive cancer cells. A negative correlation was found between expression of BCL-2 and chemosensitivity for all the 4 anticancer drugs. The inhibition rates of EADM and NVB were significantly lower in the BAD negative cancer cells than in the BAD positive cancer cells. A positive correlation was found between expression of BAD and chemosensitivity for Epirubicin.


CONCLUSIONS
The expression of BCL-2 and BAD can be used as prognosis factors of breast cancer. Detection of the BCL-2 protein expression level, particularly, combined with the detection of the expression of BCL-2 and BAD as well as ER and PR were helpful in confirming the prognosis of breast carcinoma. The combined detection of BCL-2 and BAD may be markers for predicting the responses to anticancer drugs.
Yu
Bing
B
Department of Breast and Thyroid Surgery, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong District, Chongqing, China.
Sun
Xin
X
Shen
Hong-yan
HY
Gao
Feng
F
Fan
Yuan-ming
YM
Sun
Zhi-jun
ZJ
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*
C494819:BAD protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein