MIDKINE AND PLEIOTROPHIN EXPRESSION IN NORMAL AND MALIGNANT BREAST-TISSUE

Background. Some growth factors may promote tumor growth by affecting tumor angiogenesis. The angiogenic growth factor, pleiotrophin, was de monstrated previously in human breast carcinoma tissues; however, the pattern of pleiotrophin expression in normal breast tissues has not be en established. Methods. The expression of pleiotrophin and the relate d growth factor, midkine, was examined by polymerase chain reaction am plification of reverse transcriptase copies of RNA transcripts (RT-PCR ) from freshly resected normal and malignant human breast tissues. Nor thern blot analysis of midkine expression was performed on a limited n umber of the specimens and on human and canine breast carcinoma cell l ines. Clinicopathologic variables from the breast cancer patients were examined in relation to the growth factor expression patterns. Result s. The majority of both malignant and normal breast tissues expressed pleiotrophin. In contrast, midkine was expressed frequently in the mal ignant breast tissues but in only one of the normal specimens, Norther n blot analysis of the breast carcinoma cells lines showed that they c ommonly expressed midkine transcripts. The only correlation of the gro wth factor expression patterns with the other clinical variables was t he finding that the three midkine-negative breast carcinoma specimens also had low estrogen receptor levels. Conclusions. By this analysis, the expression of pleiotrophin was equivalent in both malignant and no rmal human breast tissues. Midkine, on the other hand, exhibited incre ased expression in the breast carcinomas but showed much lower express ion in the normal breast tissue. Although the cellular source of the m idkine expression was not determined by the RT-PCR assay, the Northern blot analysis showed that isolated populations of breast cancer cells commonly express this growth factor. This is the first example of a t issue simultaneously expressing high amounts of both pleiotrophin and midkine, a finding of unclear pathophysiologic significance.