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Differential regulation of TP73 isoforms by 1α,25‐dihydroxyvitamin D3 and survivin in human colon and breast carcinomas
Author(s) -
Díaz Raquel,
GonzálezSancho José M.,
Soldevilla Beatriz,
Silva Javier,
García José M.,
García Vanesa,
Peña Cristina,
Herrera Mercedes,
Gómez Irene,
Bonilla Félix,
Domínguez Gemma
Publication year - 2010
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20821
Subject(s) - survivin , cancer research , downregulation and upregulation , gene isoform , breast cancer , context (archaeology) , colorectal cancer , western blot , cancer , medicine , biology , gene , genetics , paleontology
We evaluate whether 1,25(OH) 2 D 3 downregulates TP73 variants in colon and breast carcinomas, the role of survivin in this context, and the significance of this network in the clinic. Tumor cells were treated/untreated with 1,25(OH) 2 D 3 and transiently transfected with survivin. Levels of survivin and TP73 variants were evaluated by quantitative RT‐PCR and Western blotting. In 75 colon and 60 breast cancer patients, the expressions of survivin and TP73 isoforms were determined. Tumor characteristics were examined in each patient. Survivin protein levels were also evaluated in a subgroup of patients and cell lines. Decrease in survivin and TAp73 transcripts and protein and ΔNp73 mRNA was detected after 1,25(OH) 2 D 3 treatment. Ectopic survivin expression led to an increase in the TAp73, ΔNp73, ΔEx2p73, and ΔEx2‐3p73 transcripts. In cancer patients, direct correlations were observed between TP73 variants and survivin levels. 1,25(OH) 2 D 3 negatively regulate survivin and TP73 variants in colon and breast cancer cells. Positive regulation of TP73 isoforms by survivin may exist, which reinforces the possibility that the downregulation of TP73 forms by 1,25(OH) 2 D 3 is survivin‐dependent. © 2010 Wiley‐Liss, Inc.