Increased phospholipase D activity in human breast cancer.
Phospholipase D is believed to play an important role in cell proliferation and tumorigenesis. One of its major functions is to cause a sustained activation of protein kinase C through the primary production of phosphatidic acid from phosphatidylcholine by the enzyme, followed by dephosphorylation forming diacylglycerol. Protein kinase C is known to be activated or translocated in some tumors including breast tumors. In order to examine phospholipase D activity in breast tumors, surgical specimens of human breast tumors were obtained by mastectomy or wide excision, and their phospholipase D activities were assayed by determining the formation of phosphatidylethanol from phosphatidylcholine and ethanol. Phospholipase D activity was predominantly localized in the microsomal fraction of the tumor tissue and markedly stimulated by oleic acid. We observed a significant increase in phospholipase D activity in 17 out of 19 spontaneous human breast tumors as compared to adjacent histologically normal breast tissue. The mean specific activity in the tumors was 52.9 +/- 41.8 (SD) pmol min-1 mg protein-1 whereas the value for the normal breast tissue was 34.0 +/- 36.2 (SD) pmol min-1 mg protein-1 (P < 0.01; paired Wilcoxon's rank-sum test). The mean tumor/normal activity ratio was 2.37. Among prognostic factors, the nuclear grade, evaluated according to Schnitt et al., was found to be correlated with the activity ratio. Our results suggest a role for phospholipase D in human breast tumors. An elevation in phospholipase D activity is useful as a potential marker for malignant disease in the breast.
Uchida
N
N
First Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Okamura
S
S
Nagamachi
Y
Y
Yamashita
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology*; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D010739:Phospholipase D / Q000378:metabolism*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D010739:Phospholipase D