Die plasmainaktive Form der Pyruvatkinase (pTuM2Pk)beim Nierenzellkarzinom: ein geeigneter Tumormarker?

353

240

To better understand the molecular mechanisms that underlie the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC), we studied the gene expression profiles of 29 ccRCC tumors obtained from patients with diverse clinical outcomes by using 21,632 cDNA microarrays. We identified gene expression alterations that were both common to most of the ccRCC studied and unique to clinical subsets. There was a significant distinction in gene expression profile between patients with a relatively nonaggressive form of the disease [100% survival after 5 years with the majority (15͞17 or 88%) having no clinical evidence of metastasis] versus patients with a relatively aggressive form of the disease (average survival time 25.4 months with a 0% 5-year survival rate). Approximately 40 genes most accurately make this distinction, some of which have previously been implicated in tumorigenesis and metastasis. To test the robustness and potential clinical usefulness of this molecular distinction, we simulated its use as a prognostic tool in the clinical setting. In 96% of the ccRCC cases tested, the prediction was compatible with the clinical outcome, exceeding the accuracy of prediction by staging. These results suggest that two molecularly distinct forms of ccRCC exist and that the integration of expression profile data with clinical parameters could serve to enhance the diagnosis and prognosis of ccRCC. Moreover, the identified genes provide insight into the molecular mechanisms of aggressive ccRCC and suggest intervention strategies.

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification

Takahashi

Rhodes

Furge

et al. 2001

353

240

“…Although angiogenin expression is elevated in many types of human cancer (2)(3)(4)(5)(6)(7)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), nuclear angiogenin has so far only been reported in breast cancer tissue samples (27). The strong nuclear angiogenin staining in prostate cancer samples (Fig.…”

Section: Enhanced Expression and Nuclear Translocation Of Angiogenin Inmentioning

confidence: 99%

“…Its expression is up-regulated in various types of human cancers, including breast (2), cervical (3), colon (4), colorectal (5), endometrial (6), gastric (7), liver (8), kidney (9), ovarian (10), pancreatic (11), prostate (12), and urothelial (13) cancers, as well as astrocytoma (14), leukemia (acute myeloid leukemia and myelodysplastic syndrome) (15,16), lymphoma (non-Hodgkin's) (17), melanoma (18), osteosarcoma (19), and Wilms' tumor (20). Among them, prostate cancer, in which angiogenin expression is positively correlated with disease progression (12), is of particular interest.…”

mentioning

confidence: 99%

A therapeutic target for prostate cancer based on angiogenin-stimulated angiogenesis and cancer cell proliferation

Yoshioka

Wang

Kishimoto

et al. 2006

138

176

Human angiogenin is progressively up-regulated in the prostate epithelial cells during the development of prostate cancer from prostate intraepithelial neoplasia (PIN) to invasive adenocarcinoma. Mouse angiogenin is the most up-regulated gene in AKT-induced PIN in prostate-restricted AKT transgenic mice. These results prompted us to study the role that angiogenin plays in prostate cancer. Here, we report that, in addition to its well established role in mediating angiogenesis, angiogenin also directly stimulates prostate cancer cell proliferation. Angiogenin undergoes nuclear translocation in PC-3 human prostate cancer cells grown both in vitro and in mice. Thus, knocking down angiogenin expression in PC-3 human prostate adenocarcinoma cells inhibits ribosomal RNA transcription, in vitro cell proliferation, colony formation in soft agar, and xenograft growth in athymic mice. Blockade of nuclear translocation of angiogenin by the aminoglycoside antibiotic neomycin inhibited PC-3 cell tumor growth in athymic mice and was accompanied by a decrease in both cancer cell proliferation and angiogenesis. These results suggest that angiogenin has a dual effect, angiogenesis and cancer cell proliferation, in prostate cancer and may serve as a molecular target for drug development. Blocking nuclear translocation of angiogenin could have a combined benefit of antiangiogenesis and chemotherapy in treating prostate cancer.tumor therapy ͉ nuclear translocation ͉ ribosome biogenesis A ngiogenin is a 14-kDa angiogenic ribonuclease originally isolated from HT-29 colon adenocarcinoma cells (1). Its expression is up-regulated in various types of human cancers, including breast (2), cervical (3), colon (4), colorectal (5), endometrial (6), gastric (7), liver (8), kidney (9), ovarian (10), pancreatic (11), prostate (12), and urothelial (13) cancers, as well as astrocytoma (14), leukemia (acute myeloid leukemia and myelodysplastic syndrome) (15, 16), lymphoma (non-Hodgkin's) (17), melanoma (18), osteosarcoma (19), and Wilms' tumor (20). Among them, prostate cancer, in which angiogenin expression is positively correlated with disease progression (12), is of particular interest. Majumder et al. (21) reported that the angiogenin protein content in the serum of patients with hormone refractory prostate cancer (40 patients), in newly diagnosed prostate cancer patients (39 patients), and in control patients with no evidence of prostate cancer (37 patients) was 436 Ϯ 24, 392 Ϯ 17, and 328 Ϯ 20 ng͞ml, respectively. There is a statistically significant difference in serum angiogenin levels between the controls and untreated, hormone-naïve prostate cancer patients (P Ͻ 0.01) and between controls and hormone refractory prostate cancer patients (P Ͻ 0.001). There is also a trend toward higher levels of angiogenin in hormone refractory patients compared with newly diagnosed patients.It is known that circulating angiogenin in normal plasma is mainly produced by the liver (22) and is at a concentration of 250-350 ng͞ml (11, 13). Therefore, if the ...

“…In some cases, high tissue ANG was shown to correlate with cancer progression or poor prognosis (8,9,14). ANG levels in serum were significantly increased in patients with colorectal (15), gastric (16), pancreatic (9), ovarian (17), renal cell (18), and urothelial (13) cancer and with melanoma (19). Moreover, ANG was shown to be up-regulated by hypoxia in cultured melanoma cells but not in normal melanocytes, and the degree of induction correlated with the metastatic potential of the cell line used (12).…”

mentioning

confidence: 99%

A small-molecule inhibitor of the ribonucleolytic activity of human angiogenin that possesses antitumor activity

Kao

Jenkins

Olson

et al. 2002

113

162