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

Abstract

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 transcriptionpolymerase 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. (1) Emerging data indicate that KLKs are implicated in various human malignancies. The classical KLK gene KLK3 (also known as prostate-specific antigen) has proven to be a perfect biomarker for prostate cancer and has been used in clinical auxiliary diagnosis and prognosis prediction of prostate cancer.(2,3) Other KLK family members are overexpressed in many kinds of malignancies compared with their normal tissues, including ovarian, cervical, colorectal, gastric, lung, urinary bladder, pancreatic, and prostate cancer (KLK4, KLK11, KLK14, KLK15), but KLKs are underexpressed in breast and prostate cancers (KLK2, KLK3, KLK5, KLK6, KLK10, KLK13), renal cancer, and urinary bladder cancer.(4) KLK5 (also known as stratum corneum trypsin-like enzyme) and KLK7 (also known as stratum corneum chymotrypitc enzyme), which were originally identified from a keratinocyte cDNA library, (5)(6)(7) catalyze the degradation of intercellular cohesive structures in the outermost layer of the skin and contribute to the cell-shedding process of the skin surface, (6) which is similar to the shedding of tumor cells into the surrounding microenvironment. (8) Both KLK5 and KLK7 were reported to be overexpressed in several cancers, including ovarian, (9)(10)(11)(12)(13)(14) lung,testicular, (16,17) urinal bladder, (18) and cervi...

Down-regulation of hK7 in the sera of breast cancer and benign breast disease patients

“…Results are in accordance with the earlier studies in which significant down-regulation of KLK7 mRNA has been observed in post-menopausal breast cancer patients as compared to the pre/peri-menopausal patients [32]. However, our results are contrary to the earlier study indicating that there exists no association between KLK7 mRNA expression level and menopausal status [30].…”

“…Weak negative but statistically non-significant correlation has been observed between age of breast cancer patients and hK7. Earlier studies have shown lower expression of KLK7 mRNA in patients older than 50 years as compared to younger patients [32]. However, in the current study down regulation of hK7 was more significant in the younger patients (age below 40 years) than older patients (of age 51–60 years).…”

“…This study is the first to report the under expression of hK7 in breast carcinoma and benign breast diseases. However, down-regulation of KLK7 mRNA in breast tumors has been reported earlier [30, 32]. …”

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

“…Moreover, KLK5 and KLK7 mRNA expression levels, which are down-regulated in breast carcinomas (Li et al , 2009 ;Avgeris et al , 2011a ), were found to correlate with limited DFS and OS of breast cancer patients, unmasking in this way their unfavorable prognostic value (Yousef et al , 2002c ;Talieri et al , 2004Talieri et al , , 2011. Finally, the increased expression of KLK4 (Papachristopoulou et al , 2009 ) and KLK14 (Papachristopoulou et al , 2011 ) in breast malignancy, along with the KLK4 expression association with advanced grade and progesterone receptor-negative tumors and the association of KLK14 expression with advanced grade, large tumor size, and estrogen receptor-negative tumors, highlights their possible prognostic signifi cance for breast cancer patient ' s outcome.…”

The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma

“…These genes play different functional roles like semen liquefaction by digestion of Seminigelin by the most commonly known, KLK3, better known as prostate-specific antigen [6,7] and skin desquamation by cleaving corneodesmosomes by KLK5 and KLK7 [8]. KLKs have been implicated in different cancer types [5,6,8,9,10] and co-expression of KLK5 and KLK7 is often reported [9,11,12]. In addition, in OSCC, over-expression of KLK5, KLK7, KLK8 and KLK10 has been reported [13], but correlations with clinical and pathological parameters (especially nodal disease) were not analyzed.…”