Increased MCL-1 expression is associated with poor prognosis in ovarian carcinomas.
To investigate the potential role of the BCL-2 gene family (BAX, BCL-2, MCL-1, and BCL-XL) in ovarian cancer development and progression, mRNA expression levels of these genes were measured using semi-quantitative PCR in epithelial ovarian tumor tissues and normal ovaries. The immunohistochemical expression of MCL-1 in ovarian tumors was also examined. The expression levels of BAX and MCL-1 mRNA were significantly higher in ovarian cancers and in adenomas than in normal ovaries (P < 0.05). In contrast, the BCL-2 mRNA expression level in ovarian cancers was significantly lower than in ovarian adenomas and in normal ovaries (P < 0.05). Expression of BCL-XL mRNA was no different between normal ovaries and ovarian tumors. Log-rank testing showed that low BAX mRNA expression and high MCL-1 mRNA expression significantly correlate with poor survival for patients with stage III ovarian carcinomas (BAX, P = 0.05; MCL-1, P = 0.02). Immunohistochemical analysis showed that diffuse-positive expression of MCL-1 protein in mucinous carcinomas was significantly higher than in mucinous low malignant potential (LMP) tumors (P = 0.03). In ovarian cancer cases, diffuse-positive expression of MCL-1 protein significantly correlates with advanced clinical stage, high histologic grade, and poor survival (stage, P < 0.01; grade, P = 0.01; survival, P = 0.01). These results suggest that increased MCL-1 expression may play an important role in replacing the functions of increased BAX and decreased BCL-2 in ovarian carcinoma cells, thereby promoting cell survival, and resulting in a poor prognosis for patients with ovarian cancer.
Shigemasa
Kazushi
K
Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Minami-ku, Hiroshima 734-8551. kazu@hiroshima-u.ac.jp
Katoh
Osamu
O
Shiroyama
Yuko
Y
Mihara
Shoji
S
Mukai
Keiji
K
Nagai
Nobutaka
N
Ohama
Koso
K
D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality; D010053:Ovary / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D018076:DNA, Complementary; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein