RGD Reference Report - Transforming growth factor-beta pathway in human renal cell carcinoma and surrounding normal-appearing renal parenchyma. - Rat Genome Database

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Transforming growth factor-beta pathway in human renal cell carcinoma and surrounding normal-appearing renal parenchyma.

Authors: Cardillo, MR  Lazzereschi, D  Gandini, O  Di Silverio, F  Colletta, G 
Citation: Cardillo MR, etal., Anal Quant Cytol Histol. 2001 Apr;23(2):109-17.
RGD ID: 2299973
Pubmed: PMID:11332076   (View Abstract at PubMed)

OBJECTIVE: To analyze the role of the transforming growth factor (TGF)-beta pathway in renal tumors and to verify whether alterations in TGF-beta 1 pathway expression are associated with the grade of tumor differentiation and pathologic stage in renal cell carcinomas. STUDY DESIGN: The expression of TGF-beta 1 and TGF-beta receptors (T beta RI and T beta RII), SMAD-2 and SMAD-4 was investigated by immunohistochemistry in normal peritumoral and tumoral tissue from 53 renal cell carcinomas (clear cell type). The gene expression of SMAD-2 and SMAD-4 was also studied by reverse transcription polymerase chain reaction (RT-PCR) in normal peritumoral and tumoral tissue from 6 of 56 primary tumors. RESULTS: TGF-beta 1, T beta RI and T beta RII immunoreactivity was more frequent in tumoral than in normal peritumoral renal tissue (96.22%, 79.25% and 75.41% vs. 88.37%, 69.76% and 62.69%), whereas SMAD-2 and SMAD-4 immunoreactivity was more frequent in normal peritumoral than in tumoral tissue (23.25% and 30.23% vs. 15.09% and 7.54%). In tumor areas, immunohistochemical scores were lower for T beta RII than for T beta RI and TGF-beta 1 and higher than SMAD-4 and SMAD-2 scores. TGF-beta 1, T beta RI, T beta RII and SMAD-4 histologic scores correlated with neither the histologic grade of malignancy nor TNM clinical stage, whereas SMAD-2 protein levels were significantly lower in grade 3 than in grade 1 tumors. In the samples of normal kidney and carcinoma studied, RT-PCR detected the correct transcripts for SMAD-2 and SMAD-4, indicating that the RNA of the samples analyzed contained RNA sequences coding for these genes. CONCLUSION: Our data support the concept that the reduction of T beta RII and SMAD proteins in renal cell carcinomas is involved in tumor development and suggest an altered TGF-beta/SMAD signaling pathway in kidney neoplasia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma severityIEP 2299973; 2299973protein:decreased expression:kidneyRGD 
renal cell carcinoma severityISOSMAD2 (Homo sapiens)2299973; 2299973protein:decreased expression:kidneyRGD 
renal cell carcinoma severityISOSMAD4 (Homo sapiens)2299973; 2299973protein:decreased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Smad2  (SMAD family member 2)
Smad4  (SMAD family member 4)

Genes (Mus musculus)
Smad2  (SMAD family member 2)
Smad4  (SMAD family member 4)

Genes (Homo sapiens)
SMAD2  (SMAD family member 2)
SMAD4  (SMAD family member 4)


Additional Information