Identification of LDH-ras p21 protein complex and expression of these genes in human ovarian cancer.

Normal ovarian and ovarian cancer tissues from 35 patients were tested for LDH-A-ras protein complex formation, as well as for the expression of ras and LDH-A genes. By immunodetection of the immunoprecipitates, LDH-A-ras protein complexes are present in the homogenates of human ovarian tissues (benign and malignant). Two bands of 21 and 36 kDa were demonstrated in affinity-purified LDH active fractions by Western blot analysis, and these two proteins were proved to be ras p21 and LDH-A by immunodetection. By Northern blot analysis, elevated levels of c-Ki-ras and LDH-A mRNA transcripts were noted in 49% (17/35) and 40% (14/35) of ovarian cancers, respectively. Concurrent high expression of both genes was demonstrated in 11 cases (31%). Tyrosylphosphorylation of LDH-A was demonstrated in normal and malignant ovarian tissues, and the extent of phosphorylation was correlated with the stage of ovarian cancer. The concurrent elevated expression of ras and LDH-A in the same ovarian tissue may imply that the increased synthesis of LDH-A is due to increased or amplified signaling of the ras-cascade pathway. The possible biochemical role of the tyrosylphosphorylated LDH-A complexed with ras p21 in cell transformation and progression of human ovarian cancer is worthy of further investigation.