Bone morphogenetic proteins -2, -4, -6, -7 and their receptors are expressed in normal human kidney and renal cell carcinoma

Abstract

Bone morphogenetic proteins (BMPs) are multifunctional cytokines with important role in cell proliferation, differentiation and embryonic pattern formation. The role of BMPs in the tumor biology is under investigation. These molecules have inhibitory and stimulatory effect on growth of different cancer cells. Renal cell carcinoma (RCC) is the most lethal tumor of all urogenital cancers with increasing incidence. Because BMPs have significant influence on the renal development and pathophysiology of renal diseases it is expected that they have role in the renal cell carcinoma too. Aim of our study was to present mRNA expression of different BMPs and their receptors in RCC compared to healthy kidney tissue. We examined expression of mRNA BMP-2, mRNA BMP-4, mRNA BMP-6, mRNA BMP-7, and mRNA of their receptors (BMPR-IA, BMPR-IB, BMPR-II) in 45 RCC and 15 normal kidney tissue samples obtained by nephrectomy. Their expressions were measured by using reverse transcriptase polymerase chain reaction (RT-PCR). Relative mRNA expression were calculated by dividing the ligand or receptor expression level by the expression of GPDH and multiplied by one hundred. mRNA expression were compared between normal and neoplastic tissue and correlated with clinicopathological parameters as histological subtype, nuclear grade, TNM stage, ECOG status, gender and age. Expression of all mRNA BMP ligands and their receptors were increased in RCC specimens compared to normal kidney but these differences were not statisticaly significant. Patients with RCC were divided in two groups: clear cell (CC-RCC) and non clear cell (NCC-RCC) group. There was not differences in BMPs expression between these two groups. Expression of BMPs compared to different nuclear grade, TNM stage, ECOG status and gender was similar between investigated groups. We found higher expression of mRNA BMPR-IB in patients older than 60 years when compared with those younger than 60 years (p=0, 036). Multivariate analysis showed that expression of mRNA BMPR-IA was higher in female patients with CC-RCC (p=0, 003). These results showed that mRNA of different BMPs ligands and their receptors are present in normal human kidney cells and in tumor cells of both RCC subtypes but higher expression was noticed in tumor cells. Also their expression was not in correlation with most important clinicopathological parameters as TNM stage, nuclear grade and histological subtype.