RGD Reference Report - Expression of mutant thyroid hormone nuclear receptors is associated with human renal clear cell carcinoma. - Rat Genome Database

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Expression of mutant thyroid hormone nuclear receptors is associated with human renal clear cell carcinoma.

Authors: Kamiya, Y  Puzianowska-Kuznicka, M  McPhie, P  Nauman, J  Cheng, SY  Nauman, A 
Citation: Kamiya Y, etal., Carcinogenesis. 2002 Jan;23(1):25-33.
RGD ID: 2315097
Pubmed: PMID:11756220   (View Abstract at PubMed)

Thyroid hormone (T(3)) regulates proliferation and differentiation of cells, via its nuclear receptors (TRs). These processes have been shown to be abnormally regulated during carcinogenesis. We have previously found aberrant expression of TRalpha and TRbeta mRNAs in renal clear cell carcinoma (RCCC), suggesting possible involvement of TRs in the carcinogenesis of RCCC. To understand the molecular actions of TRs in RCCC, cDNAs for TRbeta1 and TRalpha1 were cloned from 22 RCCC tissues and 20 surrounding normal tissues. Mutations were found in seven TRbeta1 and three TRalpha1 cDNAs. Two TRbeta1 cDNAs had a single mutation, while five TRbeta1 and three TRalpha1 had two or three mutations. Most of the mutations were localized in the hormone-binding domain. Using the TRs prepared by in vitro transcription/translation, we found that these mutations led to a loss of T(3) binding activity and/or impairment in binding to thyroid hormone response elements (TREs). Furthermore, nuclear extracts from RCCC tissues also exhibited impairment in binding to TREs. These results indicate that the normal functions of TRs in RCCC tissues were impaired. Together with the aberrant expression patterns, these mutated TRs could contribute to the carcinogenesis of RCCC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma  IAGP 2315097; 2315097DNA:mutations (human)RGD 
renal cell carcinoma  ISOTHRA (Homo sapiens)2315097; 2315097DNA:mutations (human)RGD 
renal cell carcinoma  ISOTHRB (Homo sapiens)2315097; 2315097DNA:mutations (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Thra  (thyroid hormone receptor alpha)
Thrb  (thyroid hormone receptor beta)

Genes (Mus musculus)
Thra  (thyroid hormone receptor alpha)
Thrb  (thyroid hormone receptor beta)

Genes (Homo sapiens)
THRA  (thyroid hormone receptor alpha)
THRB  (thyroid hormone receptor beta)


Additional Information