Bcl-2 phosphorylation has pathological significance in human breast cancer

Pathobiology. 2006;73(4):205-12. doi: 10.1159/000096022.

Abstract

The anti-apoptotic molecule, Bcl-2, is well known to play an important role in the chemoresistance of breast cancer. We have previously demonstrated that phosphorylation of Fas-associated death domain-containing protein (FADD) at 194 serine through c-jun NH2-terminal kinase (JNK) activation sensitizes breast cancer cells to chemotherapy through accelerating cell cycle arrest at G2/M, and that Bcl-2 phosphorylation downstream of JNK/FADD plays an important role in cell growth suppression by paclitaxel. In this study, the clinicopathological association of phosphorylated Bcl-2 (P-Bcl-2) with estrogen, progesterone, c-erbB-2 receptors, p53 expressions and phosphorylated FADD/JNK (P-FADD/JNK) was analyzed immunohistochemically using 107 human breast cancer specimens. Expression of P-Bcl-2 was found to significantly correlate with lymphatic invasion, lymph node metastasis, but not histological differentiation, tumor grade or vascular and fatty invasion. The positivity of P-Bcl-2 was also significantly correlated to that of P-FADD/JNK. Thus, P-Bcl-2 as well as the P-FADD/JNK parameter might be useful markers for cancer progression, independent of the hormone receptor status, in human breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / secondary
  • Female
  • Humans
  • Immunoenzyme Techniques
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Phosphorylation
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • JNK Mitogen-Activated Protein Kinases