Adrenomedullin and its receptors expression in renal tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10568-10568
Author(s):  
J. Deville ◽  
S. Salas ◽  
C. Bartoli ◽  
C. Dupuis ◽  
F. Duffaud ◽  
...  

10568 Background: Adrenomedullin (AM) is a 52 amino acid peptide that has an important role on tumor cell proliferation and neoangiogenesis through its receptors CRLR/RAMP2 and CRLR/RAMP3. AM gene expression is stimulated by Hypoxia Inductible Factor-1 (HIF- 1) and 60–80% of the human conventional renal carcinomas (cRCC) display mutations in the tumor suppressor protein von Hippel-Lindau, which leads to constitutively elevated HIF-1. Methods: Tumors and non-malignant kidney tissues were obtained from patients who underwent unilateral nephrectomy. We studied VEGFA, AM and its receptors expression by quantitative RT-PCR in 62 frozen renal tumors including: 40 cRCC; 5 cRCC metastasis; 5 chromophobe carcinomas; 5 Papillary carcinomas; 2 oncocytomas; 2 collecting duct carcinomas; 2 normal adjacent renal tissue; 1 unclassified renal tumor. AM and AM-receptors expression was studied in 42 paraffin-embedded renal tumors by immunohistochemistry using rabbit anti-AM, anti-CRLR, anti-RAMP2 and anti-RAMP3 polyclonal antibodies. Effects of these anti AM or anti AM- receptors antibodies on cell proliferation were examined in vitro on BIZ cell line (cRCC cells). Results: VEGFA, AM and AM-receptors genes were overexpressed in cRCC compared to other renal tumors (Except AM gene in chromophobe carcinoma). Their expressions were independent of classical prognostic factors (such as Fuhrman Grade and pT status). In cRCC, there was a strong positive correlation between VEGF-A gene expression and AM (r=0.7; p=0.01) and AM-receptors genes expressions (RAMP2 r=0.61; p= 0.01 and RAMP3 r=0.58; p= 0.01). Immunohistochemistry confirmed a tumor expression of CRLR, RAMP2 and AM in more than 80% cRCC. RAMP3 was expressed by inflammatory cells but not by tumoral cells. The cell proliferation assay showed a significant inhibition of BIZ cell proliferation by AM antibody or AM-receptors antibodies. Conclusion: AM and its receptor CRLR/RAMP2 are overexpressed in cRCC. In vitro cell proliferation assay results support that AM inhibition may suppress cRCC growth, independently of potential antiangiogenic effects. Further studies on animal models are needed but AM pathway may be a potential therapeutic target in cRCC. No significant financial relationships to disclose.

1994 ◽  
Vol 114 (5) ◽  
pp. 316-324 ◽  
Author(s):  
Keiji IMAI ◽  
Reiko UKAI ◽  
Kazuhiro ISHIKAWA ◽  
Hiromoto AOKI ◽  
Tetsuo KATO ◽  
...  

2003 ◽  
Vol 26 (8) ◽  
pp. 1219-1224 ◽  
Author(s):  
Tomoko Okubo ◽  
Toshinari Suzuki ◽  
Yoshiko Yokoyama ◽  
Kazutaka Kano ◽  
Itsu Kano

2021 ◽  
Vol Volume 13 ◽  
pp. 443-449
Author(s):  
Pratiwi Soesilawati ◽  
Andra Rizqiawan ◽  
Retno Indrawati Roestamadji ◽  
Ahmad Rizal Arrosyad ◽  
Muhammad Alwino Bayu Firdauzy ◽  
...  

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.


Author(s):  
Rehab Elfadul ◽  
Roman Jesien ◽  
Ahmed Elnabawi ◽  
Paulinus Chigbu ◽  
Ali Ishaque

Contaminants of Emerging Concern (CECs) with estrogenic or estrogenic-like activity have been increasingly detected in aquatic environments and have been an issue of global concern due to their potential negative effects on wildlife and human health. This study used the MCF-7 cell proliferation assay (E-Screen) to assess the estrogenic activity profiles in Maryland Coastal Bays (MCBs), a eutrophic system of estuaries impacted by human activities. Estrogenic activity was observed in all study sites tested. Water samples from MCBs increased MCF-7 cell proliferation above the negative control from 2.1-fold at site 8, located in Sinepuxent Bay close to the Ocean City Inlet, to 6.3-fold at site 6, located in Newport Bay. The proliferative effects of the sediment samples over the negative control ranged from 1.9-fold at the Assateague Island National Seashore site to 7.7-fold at the Public Landing site. Moreover, elevated cell proliferation (p < 0.05) was observed when cells were co-exposed with 17ß-Estradiol (E2), while reduction in cell proliferation was observed when cells were co-exposed with the antagonist ICI 182, 780 suggesting that cell proliferative effects were primarily mediated by the estrogen receptor (ER). These results suggest the occurrence of some estrogenic or hormonal-like compounds in the MCBs and are consistent with our previous findings based on vitellogenin analyses.


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