Increased levels of nm23 H1/nucleoside diphosphate kinase A mRNA associated with adenocarcinoma of the prostate

Abstract

Overexpression of the nm23H1 gene has been associated with the suppression of metastasis in several solid tumors. However, in colorectal carcinoma and neuroblastoma, increased levels of nm23 H1 nucleoside diphosphate kinase A (NDPKA) mRNA are associated with tumorigenesis. To determine the role of rim23 H1/ NDPKA in the prostate, normal and/or malignant tissue samples from 29 consecutive patients were studied. Levels of rim23 H1/NDPKA mRNA and nm23 H1/NDPKA mRNA protein were determined in tissue from 18 and 27 patients, respectively. In all, 16 of the 18 tumor samples expressed increased levels of nm23 H1/NDPKA mRNA as compared with those measured in normal tissue. The level of rim23 H1/NDPKA mRNA was > 10-fold higher in a metastatic lymph node than in normal prostate tissue. All cancer specimens and areas of prostatic intraepithelial neoplasia showed immunoreactivity with the nm23 H1/ NDPKA antibody; however, normal prostatic tissue was unreactive. These findings suggest that overexpression of the rim23 H1/NDPKA gene occurs frequently in adenocarcinomas of the prostate and may be an early event in prostate cancer tumorigenesis.Over the last 15 years, adenocarcinoma of the prostate has become the most common cancer of men in the United States, with the estimated incidence being 23% [2]. Prostate cancer accounts for more than 12% of cancer deaths among men, and the mortality associated with this malignancy in men is second only to that of lung cancer. This high death rate occurs despite the observation that prostate cancer is being identified at an earlier clinical stage through aggressive screening studies [3]. Therefore, biological events rather than clinical stage alone are important in the formation of metastases.Correspondence to: D. P. Wood, Jr.; Fax: +1 (606) Tumorigenicity and metastatic potential are related to a series of complex independent and linked sequential events [5]. The formation of metastases required cellular transformation, invasion through the basement membrane, cell motility, penetration of the vascular and/or lymphatic beds, angiogenesis, and proliferation at distant sites [6,15]. Altering the ability of a cell to perform any of these activities would suppress the metastatic potential of that cell. Steeg et al. [20], in an attempt to identify the genes involved in suppressing or promoting metastasis, performed differential colony hybridization of mRNA between melanoma cell lines with low and high metastatic potentials. These experiments resulted in the discovery of a potential metastatic suppressor gene, rim23 H1, with low levels of nm23 H1 mRNA expression being found in highly metastatic melanoma cell lines and higher levels occurring in cell lines with low metastatic potential [20]. Additional experiments determined that rim23 H1 is part of a gene family, and two nm23 genes have been identified: rim23 H1 and nm23 H2. The gene product of nm23 H1 is nucleoside diphosphate kinase A (NDPKA) [7], whereas that of nm23 H2 is nucleoside diphosphate kinase B [7,19].Various human tumor tissues ha...

Molecular biology of prostate cancer

“…266,267 Another study found that, unlike breast cancer and melanoma in which decreased NM23 is associated with metastases, overexpression of the NM23 gene occurs frequently in adenocarcinoma of the prostate and may even be an early event of PC tumorigenesis. 268 Levels of NM23 mRNA and protein were both increased in metastatic PC lymph nodes compared to normal prostate tissue. Furthermore, cancer specimens and adjacent PIN showed immunoreactivity with NM23 antibody, but there was weak or no reactivity in normal prostatic tissue.…”

“…Furthermore, cancer specimens and adjacent PIN showed immunoreactivity with NM23 antibody, but there was weak or no reactivity in normal prostatic tissue. 267,268 More work is thus needed to clarify the role and clinical implications of NM23 in PC.…”

Prostate cancer: are new prognostic markers on the horizon?

“…44 In clinically signi®cant CaP it has been found that nm23-H1 mRNA levels were more than 10-fold higher than levels found in latent CaP or normal prostates, which increased with tumour grade. 45,46 Strong nm23-H1 immunostaining is also frequently found in malignant cells of localized CaPs and metastatic sites of CaP. 47,48 Although encouraging, further studies of the contribution of nm23 regulation in loss of metastasis suppression in CaP are needed.…”

Evidence for interaction between human PRUNE and nm23-H1 NDPKinase

“…Low levels of the nm23-H1 gene expression increase metastatic potentials in a variety of tumour types and transfected cells (Betke et al, 1998;de la Rosa et al, 1995;Guo et al, 1998;Hartsough and Steeg, 1998;Russell et al, 1998;Tagashira et al, 1998;Yoshida et al, 1998;. However, numerous tumours and highly proliferative cells overexpress the nm23-H1 gene (Chang et al, 1994;Gazzeri et al, 1996;Jensen et al, 1996;Keim et al, 1992;Leone et al, 1993;Muller et al, 1998;Sastre-Garau et al, 1992a;Shimada et al, 1998). These results suggest an overexpression of nm23-H1 linked to early stages of cancer and a loss of expression in more advanced stages.…”