Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia

Abstract

Summary There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen Prostate cancer is the third most common malignancy in men in England and Wales (OPCS-Cancer Statistics, 1985). Of the 9,000 patients that present every year, approximately 50% are already suffering from metastatic disease, one of the major causes of their mortality (Whitmore, 1984 Thompson, 1990).An important group of bone-inducing factors are the bone morphogenetic proteins which have the capacity to induce new bone formation when implanted ectopically into experimental animals (Urist, 1965). Seven BMPs have so far been identified and, with the exception of BMP-1, they are all members of the TGF-P superfamily (Celeste et al., 1990; Wozney et al., 1988;Wozney, 1989). To date there has been no examination of BMP gene expression in prostatic tissue.The aims of this study were 2-fold. Firstly, to establish whether prostatic tissue and prostatic cell lines expressed the genes for BMPs. Secondly, to examine the pattern of BMP expression in patients with benign prostatic hyperplasia, and metastatic and non-metastatic prostatic adenocarcinoma in order to determine whether any differences in expression were related to the tumorigenic and metastatic phenotype of the prostatic cancer. The expression of BMPs one to six has been determined by mRNA phenotyping (Brenner et al., 1989) utilising specifically designed oligonucleotide primers selected for non-homologous regions of the BMPs. Materials and methods PatientsForty-one patients were studied. The study was approved by the ethics committee and informed consent was obtained from each patient prior to entering the study. Nineteen men had histologically proven prostatic adenocarcinoma, 11 of whom had skeletal metastases as shown by a positive technetium 99-m bone scan. Twelve patients had known benign prostatic hyperplasia (BPH) and 10 others had ocular melanomas and were used as controls, since ocular melanomas rarely metastasise to the bony skeleton and such metastases are a very late phenomenon. None of the 10 ocular melanoma patients had bony metastases. Prostatic tissue samples were obtained from transurethral resection specimens or by transrectal needle core biopsy, and ocular melanoma samples were obtained following enucleation. The nature of each sample was confirmed by standard histological examination, and graded using the Gleason scoring system (Gleason et al., 1974). Samples were snap frozen in liquid nitrogen immediately after removal and stored at -70°C prior to RNA extraction. Cell linesTwo well characterised mycoplasma-free human prostate cell lines, PC-3 (Kaighn et al., 1979) and DU145 (Stone et al., 1978), were used. Cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (FCS), glutamine, penicillin and streptomycin. The...

Autotaxin–lysophosphatidic acid– LPA 3 signaling at the embryo‐epithelial boundary controls decidualization pathways

“…Thus, LPA–LPA 3 signaling is critical in the development of endometriosis. Furthermore, HB‐EGF, COX‐2, and Wnt4 as well as Bmp2 have been shown to be risk factors for sex hormone‐dependent diseases, such as prostatic hyperplasia, breast cancer, and ovarian cancer (Bentley et al , 1992; Ferrandina et al , 2002; Levin, 2003; Zong et al , 2012). Since LPA 3 is highly expressed in the prostate, mammary gland, and ovary (Bandoh et al , 1999), LPA 3 signaling might contribute to the progression of such diseases.…”

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

“…19 In the tumor tissue microarray, low levels of BMP4 protein expression were detected in cancers of the prostate and brain that have only been shown to express BMP4 at the mRNA level. 45,46 For malignancies originating from the thyroid, uterus, spleen and lymph nodes, this is the first study to examine BMP4 protein expression in these tissues.…”

Bone morphogenetic protein-6: potential mediator of osteoblastic metastases in prostate cancer

“…Most signi®cantly, BMP-6 was the only protein that was not expressed in the non-metastatic group but was in 55% of patients with established skeletal metastases. 7 BMP-6 mRNA and protein expression was subsequently investigated in malignant and benign prostatic tissue using in situ hybridization and immunohistochemistry. 8 This study showed that mRNA for BMP-6 was exclusively detected in the cytoplasm of malignant prostatic epithelial cells, with no signals in the prostatic stroma.…”