Midkine and pleiotrophin expression in normal and malignant breast tissue

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Abstract
Background. Some growth factors may promote tumor growth by affecting tumor angiogenesis. The angiogenic growth factor, pleiotrophin, was demonstrated previously in human breast carcinoma tissues; however, the pattern of pleiotrophin expression in normal breast tissues has not been established. Methods. The expression of pleiotrophin and the related growth factor, midkine, was examined by polymerase chain reaction amplification of reverse transcriptase copies of RNA transcripts (RT-PCR) from freshly resected normal and malignant human breast tissues. Northern blot analysis of midkine expression was performed on a limited number of the specimens and on human and canine breast carcinoma cell lines. Clinicopathologic variables from the breast cancer patients were examined in relation to the growth factor expression patterns. Results. The majority of both malignant and normal breast tissues expressed pleiotrophin. In contrast, midkine was expressed frequently in the malignant breast tissues but in only one of the normal specimens. Northern blot analysis of the breast carcinoma cells lines showed that they commonly expressed midkine transcripts. The only correlation of the growth factor expression patterns with the other clinical variables was the finding that the three midkine-negative breast carcinoma specimens also had low estrogen receptor levels. Conclusions. By this analysis, the expression of pleiophin was equivalent in both malignant and normal human breast tissues. Midkine, on the other hand, exhibited increased expression in the breast carcinomas but showed much lower expression in the normal breast tissue. Although the cellular source of the midkine 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 tissue simultaneously expressing high amounts of both pleiotrophin and midkine, a finding of unclear pathophysiologic significance.