Parallel underexpression of kallikrein 5 and kallikrein 7 mRNA in breast malignancies

Kallikrein (KLK) 5 and KLK7 were reported to be overexpressed in several cancers, but underexpressed in prostate and breast cancers. However, the expression levels of KLK5 and KLK7 in benign breast tissues and metastases, and the relationship between KLK5 and KLK7, have not been reported. In addition, the value of KLK5 and KLK7 in the diagnosis and prognosis prediction of breast cancer patients is far from clear. To further determine their role and clinical significance in breast cancer and to explore the relationship between KLK5 and KLK7, the mRNA levels of KLK5 and KLK7 in normal breast tissues, benign breast tissues, primary tumors, and lymph node metastases were detected by real‐time reverse transcription–polymerase chain reaction and microarray. The relationship between KLK5 and KLK7 expression and clinicopathological parameters, and the correlation between the mRNA levels of KLK5 and KLK7 as well as the 5′‐uncoding regions of KLK5 and KLK7 were analyzed. The mRNA levels of KLK5 and KLK7 were both downregulated in breast cancers relative to normal and benign tissues, and downregulated in metastases compared to primary cancers. Underexpression of KLK5 and KLK7 was correlated with postmenopausal status and positive estrogen receptor status. The mRNA levels of KLK5 and KLK7 were positively correlated in breast malignancies. Moreover, four homologous sequences and 10 transcription factors as potential regulators were found on the control regions of both KLK5 and KLK7. Thus, KLK5 and KLK7 were underexpressed in parallel, potentially with the same regulation pathways, in breast malignancies, which might contribute to the carcinogenesis and development of breast cancer. They are potential biomarkers for breast cancer. ( Cancer Sci 2009; 100: 601–607)