Differential regulation of TP73 isoforms by 1α,25‐dihydroxyvitamin D3 and survivin in human colon and breast carcinomas

Díaz, Raquel; González‐Sancho, José Manuel; Soldevilla, Beatriz; Silva, Javier; García, José M.; Garcı́a, Vanesa; Peña, Cristina; Herrera, Mercedes; Gómez, Irene; Bonilla, Félix; Domínguez, Gemma

doi:10.1002/gcc.20821

Cited by 8 publications

(6 citation statements)

References 42 publications

(49 reference statements)

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“…Seventy percent of TAp73 knock-out mice or mice heterozygous for p73 suffer from malignant tumors. Colorectal and breast cancer predominantly show an increase in ΔNp73 ( 170 ). Overexpression of both, TA and ΔN isoforms, has been detected in thyroid cancer and in chronic B-cell leukemia ( 171 ), whereas diminished p73 expression has been reported for pancreatic malignancies ( 172 ).…”

Section: P73 and Its Isoformsmentioning

confidence: 99%

p53 Family and Cellular Stress Responses in Cancer

2014

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p53 is an important tumor suppressor gene, which is stimulated by cellular stress like ionizing radiation, hypoxia, carcinogens, and oxidative stress. Upon activation, p53 leads to cell-cycle arrest and promotes DNA repair or induces apoptosis via several pathways. p63 and p73 are structural homologs of p53 that can act similarly to the protein and also hold functions distinct from p53. Today more than 40 different isoforms of the p53 family members are known. They result from transcription via different promoters and alternative splicing. Some isoforms have carcinogenic properties and mediate resistance to chemotherapy. Therefore, expression patterns of the p53 family genes can offer prognostic information in several malignant tumors. Furthermore, the p53 family constitutes a potential target for cancer therapy. Small molecules (e.g., Nutlins, RITA, PRIMA-1, and MIRA-1 among others) have been objects of intense research interest in recent years. They restore pro-apoptotic wild-type p53 function and were shown to break chemotherapeutic resistance. Due to p53 family interactions small molecules also influence p63 and p73 activity. Thus, the members of the p53 family are key players in the cellular stress response in cancer and are expected to grow in importance as therapeutic targets.

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Section: P73 and Its Isoformsmentioning

confidence: 99%

p53 Family and Cellular Stress Responses in Cancer

2014

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“…(2010) conducted a translational study to evaluate whether 1,25(OH)(2) vitamin D(3) downregulates TP73 variants in colon and breast cancers (Diaz 2010). They reported that ectopic survivin expression led to an increase in all of the TAp73, ΔNp73, ΔEx2p73, and ΔEx2-3p73 transcripts.…”

Section: Aberrant Expression Altered Splicing and Mutations Of P63 mentioning

confidence: 99%

Alterations of p63 and p73 in Human Cancers

Inoue

Fry

2014

Subcellular Biochemistry

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Summary p53 and its related genes, p63 and p73 constitute the p53 gene family. While p53 is the most frequently mutated gene in human tumors, p63 and p73 are rarely mutated or deleted in cancers. Many studies have reported p63/p73 overexpression in human cancers while others showed that a loss of p63/p73 is associated with tumor progression and metastasis. Thus, whether p63 or p73 is a tumor suppressor gene or an oncogene has been a matter of debate. This controversy has been attributed to the existence of multiple splicing isoforms with distinct functions; the full-length TA isoform of p63 has structural and functional similarity to wild-type p53, whereas the ΔNp63 acts primarily in dominant-negative fashion against all family members of p53. Differential activities of TA and ΔN isoforms have been shown in vivo by creating isoform-specific gene knockout mice. All p53, p63, p73 proteins bind to and activate target genes with p53-response elements; p63 also binds to distinct p63-response elements and regulate expression of specific target genes involved in skin, limb, and craniofacial development. Interestingly, several studies have shown that both p63 and p73 are involved in cellular response to cancer therapy and others have indicated that both of these molecules are required for p53-induced apoptosis, suggesting functional interplay among p53 family proteins. Consistent with these findings, aberrant splicing that result in ΔNp63 or ΔNp73 overexpression are frequently found in human cancers, and is associated with poor clinical outcomes of patients in the latter. Thus immunohistochemical staining of tumor specimen with ΔNp73-specific antibody might have diagnostic values in cancer clinics.

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“…Vitamin D3 inhibits survivin and TP73 isoforms in colon and breast carcinomas. In vitro and in vivo approaches speculate that the downregulation of TP73 isoforms by 1,25(OH)2D3 could be survivin-dependent [52] . Research is still in progress in order to design new agents aiming survivin either at the genomic level or at the protein level.…”

Section: Chemotherapy and Survivinmentioning

confidence: 99%

Association of survivin splice variants with prognosis and treatment of breast cancer

Pavlidou

Kroupis

Dimas

2014

WJCO

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The purpose of this study was the overview of current knowledge regarding the use of survivin and its isoforms in prognosis and treatment of breast cancer. An advanced search of Medline was performed using the following search strategy: "(survivin isoforms) OR (survivin transcript variants) AND (breast cancer) AND (neoplasm OR tumor OR cancer OR carcinoma)". Relevant studies were retrieved and processed thoroughly in order to analyze the related data. Besides wild-type survivin full-length transcript, another six splice variants have been identified. Overexpression of survivin and its isoforms leads to shorter overall and disease-free survival; the transcript variants are correlated with apoptosis and could assist prognosis prediction. It has been proved through numerous studies that inhibiting survivin isoforms might become a promising target of drug therapy of carcinomas. Use of small molecule YM155 could offer new therapy for triple negative breast cancer patients, while, chemotherapy with 5-fluorouracil + epirubicin + cyclophosphamide and Tax-Epi could be guided by survivin splice variants measurements. Survivin transcript variants could become prognostic biomarkers and could provide information about clinical management of patients suffering from breast cancer.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Survivin gene; Isoforms; Therapy; Prognosis; Breast cancer Core tip: Besides wild type survivin full length transcript, another six splice variants have been identified. Overexpression of survivin and its isoforms leads to shorter overall and disease-free survival; the transcript variants are positively correlated with apoptosis and could assist prognosis prediction. It has been proved through numerous studies that inhibiting survivin isoforms might become a promising target of drug therapy of carcinomas. Use of small molecule YM155 could offer new therapy for triple negative breast cancer patients while, chemotherapy with 5-fluorouracil + epirubicin + cyclophosphamide and Tax-Epi could be guided by survivin splice variants measurements. Survivin transcript variants could become prognostic biomarkers and could provide information about clinical management of patients suffering from breast cancer.Pavlidou A, Kroupis C, Dimas K. Association of survivin splice variants with prognosis and treatment of breast cancer. World J

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Differential regulation of TP73 isoforms by 1α,25‐dihydroxyvitamin D3 and survivin in human colon and breast carcinomas

Cited by 8 publications

References 42 publications

p53 Family and Cellular Stress Responses in Cancer

p53 Family and Cellular Stress Responses in Cancer

Alterations of p63 and p73 in Human Cancers

Association of survivin splice variants with prognosis and treatment of breast cancer

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