Increased MCL-1 expression is associated with poor prognosis in ovarian carcinomas

Jpn J Cancer Res. 2002 May;93(5):542-50. doi: 10.1111/j.1349-7006.2002.tb01289.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • DNA, Complementary / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / physiology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovary / metabolism
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Time Factors
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • BAX protein, human
  • BCL2L1 protein, human
  • DNA, Complementary
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • bcl-X Protein