Midkine and pleiotrophin expression in normal and malignant breast tissue

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.

Immunohistochemical and In Situ Hybridization Analyses of Midkine Expression in Thyroid Papillary Carcinoma

“…Breast and lung carcinomas, as well as glioblastomas, have different origins. However, these malignant tumor tissues overexpressed MK mRNA, whereas the corresponding noncancerous normal tissues did not (11,12,14). Our results regarding MK mRNA overexpression in thyroid papillary carcinomas coincide with those of the carcinomas originated from the different organs mentioned above.…”

“…In gastric and colorectal carcinomas, the MK mRNA level was higher in cancer specimens than in the corresponding noncancerous tissues (13). Although normal breast and lung tissues did not express MK mRNA, it was frequently expressed in malignant breast and lung tissues (11,12). In our recent study of brain tumors, glioblastomas expressed MK mRNA strongly, although normal brain tissues did not (14).…”

Promotion of self-renewal of embryonic stem cells by midkine

“…However, further research is needed to assess the function and mechanism of midkine in the embryonic stem cell culture system. MK expression is up-regulated in the majority of human tumors, including neuroblastomas [44] , head and neck cancer, esophageal cancer, lung cancer [9] , breast cancer [45] , bladder cancer [46] , Wilms' tumor, gastrointestinal cancers [10][11] and a variety of tumor-derived cell lines [9-10, 45, 47, 48] . However, the expression of MK is highly restricted in normal adult tissues, making it a potential marker for cancers.…”

The Multifunctional Growth Factor Midkine Promotes Proliferation and Migration in Pancreatic Cancer

“…Previous studies have revealed that expression of midkine (MK) plays an important role in different aspects of tumor progression in diverse solid tumors (6)(7)(8). We have recently shown that high mRNA and protein expression of MK in PDAC protected cancer cells from chemotherapy-induced apoptosis.…”