Biological Significance of C-met Over Expression in Papillary Renal Cell Carcinoma

Sweeney, Paul; El‐Naggar, Adel K.; Lin, Sue Hwa; Pisters, Louis L.

doi:10.1016/s0022-5347(05)64830-6

Cited by 67 publications

(40 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most tumors with strong c-Met expression were found to have a serous papillary histology, but 3 of 10 clear cell cancers showed strong c-Met expression, suggesting that c-Met is highly expressed in this rare but clinically aggressive histologic subtype. This finding expands on those of previous studies that have reported the expression of c-Met in clear cell cancers (32) and renal cell cancer, which resembles clear cell cancer in its histologic appearance (33). Yet, although we believe that we have established c-Met overexpression as a marker for human ovarian cancer, we are aware that the percentage of patients with strong c-Met expression (11%) may seem too low to justify developing c-Met as a therapeutic target.…”

Section: Discussionsupporting

confidence: 89%

c-Met Overexpression Is a Prognostic Factor in Ovarian Cancer and an Effective Target for Inhibition of Peritoneal Dissemination and Invasion

et al. 2007

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 89%

c-Met Overexpression Is a Prognostic Factor in Ovarian Cancer and an Effective Target for Inhibition of Peritoneal Dissemination and Invasion

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Because all biological activities of HGF are mediated by a single receptor, the expression and levels of c-met protein not only determine the cell-type specificity of HGF actions but also dictate the overall activities of this paired signaling system. Consistent with this view, earlier studies indicate that it is the abundance and activity of c-met receptor, rather than HGF itself, that best correlate with the biological function of HGF in diverse organs under physiological and pathological conditions (8,28,39).…”

mentioning

confidence: 67%

Suppression of HGF receptor gene expression by oxidative stress is mediated through the interplay between Sp1 and Egr-1

Zhang

Liu

2003

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Hepatocyte growth factor (HGF) receptor, the product of the c-metprotooncogene, is transcriptionally regulated by a wide variety of cytokines as well as extracellular environmental cues. In this report, we demonstrate that c-met expression was significantly suppressed by oxidative stress. Treatment of mouse renal inner medullary collecting duct epithelial cells with 0.5 mM H2O2inhibited c-met mRNA and protein expression, which was concomitant with induction of Egr-1 transcription factor. Ectopic expression of Egr-1 in renal epithelial cells markedly inhibited endogenous c-met expression in a dose-dependent fashion, suggesting a causative effect of Egr-1 in mediating c-met suppression. The cis-acting element responsible for H2O2-induced c-met inhibition was localized at nucleotide position −223 to −68 of c-met promoter, in which reside an imperfect Egr-1 and three Sp1-binding sites. Egr-1 markedly suppressed c-met promoter activity but did not directly bind to its cis-acting element in the c-met gene. Induction of Egr-1 by oxidative stress attenuated the binding of Sp1 to its cognate sites, but it did not affect Sp1 abundance in renal epithelial cells. Immunoprecipitation uncovered that Egr-1 physically interacted with Sp1 by forming the Sp1/Egr-1 complex, which presumably resulted in a decreased availability of unbound Sp1 as a transcriptional activator for the c-met gene. Thus it appears that inhibition of c-met expression by oxidative stress is mediated by the interplay between Sp1 and Egr-1 transcription factors. Our findings reveal a novel transcriptional regulatory mechanism by which Egr-1 sequesters Sp1 as a transcriptional activator of c-met via physical interaction.

show abstract

“…For example, MET mutations are very rare in patients with sporadic papillary cancer (25). Although immunohistochemical-based expression of c-MET has been described in the sporadic forms of papillary renal cell carcinoma, the physiologic relevance of this finding remains unclear (26). The BHD gene is occasionally inactivated in spontaneous renal cell carcinomas of various subtypes, but once again whether this is important to the malignant phenotype remains unknown (27).…”

Section: Genetics and Biologymentioning

confidence: 99%

Therapeutic Options for Variant Renal Cancer

Stadler

2004

Clinical Cancer Research

View full text Add to dashboard Cite

Variant or nonclear cell renal cell cancer is a rare disease constituting only ϳ5% to 8% of the metastatic renal cell cancer population. Pathological criteria for the three main variant subtypes, papillary, chromophobe, and collecting duct, have been specified. Nonetheless, there may be subtypes within these variants, many poorly differentiated tumors cannot be reliably classified, and expertise in recognizing specific subtypes is not widespread. Expression analysis and other molecular techniques are beginning to clarify and standardize the pathological classification scheme. Because these classifications are relatively new and the number of patients with any one subtype is limited, little is known about appropriate therapies for patients with metastatic disease. Retrospective series strongly suggest that immunotherapy is not effective in any nonclear cell subtype. Case reports suggest that cytotoxic chemotherapy used for transitional cell cancers may be helpful in patients with collecting duct cancers. A central registry of patients with variant renal cell cancer should be created in which response to various therapies is recorded. Such a registry could provide support for a more formal multi-institutional study investigating a specific drug or regimen.

show abstract

Biological Significance of C-met Over Expression in Papillary Renal Cell Carcinoma

Abstract: Our study indicates that c-met over expression may be associated with an aggressive phenotype in these tumors.

Cited by 67 publications

References 24 publications

c-Met Overexpression Is a Prognostic Factor in Ovarian Cancer and an Effective Target for Inhibition of Peritoneal Dissemination and Invasion

c-Met Overexpression Is a Prognostic Factor in Ovarian Cancer and an Effective Target for Inhibition of Peritoneal Dissemination and Invasion

Suppression of HGF receptor gene expression by oxidative stress is mediated through the interplay between Sp1 and Egr-1

Therapeutic Options for Variant Renal Cancer

Contact Info

Product

Resources

About