drives invasion through expression of its Δ133p53β variant.

is conventionally thought to prevent cancer formation and progression to metastasis, while mutant has transforming activities. However, in the clinic, mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of mutation status.

Uncovering the role of p53 splice variants in human malignancy: a clinical perspective.

Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field.

Detecting p53 isoforms at protein level.

The human p53 protein isoforms are expressed in several cell lines and modulate p53 tumor suppressor -activity, mainly through modulation of gene expression (1-4). Thus, identifying the pattern of p53 isoforms expression in cell lines is a key step for future studies of the p53 network (5). At the moment, the detection of p53 protein isoforms is based on the use of a panel of antibodies allowing their identification by comparing their molecular weights and their detection pattern by different antibodies (6).

Detecting and quantifying p53 isoforms at mRNA level in cell lines and tissues.

The TP53 gene expresses at least nine different mRNA variants (p53 isoform mRNAs), including the one encoding the canonical p53 tumor suppressor protein. We have developed scientific tools to specifically detect and quantify p53 isoform expression at mRNA level by nested RT-PCR (reverse transcription-polymerase chain reaction) and quantitative real-time RT-PCR (RT-qPCR using the TaqMan(®) chemistry). Here, we describe these two methods, while highlighting essential points with regard to the analysis of p53 isoform mRNA expression.

p53 Isoforms: An Intracellular Microprocessor?

Normal function of the p53 pathway is ubiquitously lost in cancers either through mutation or inactivating interaction with viral or cellular proteins. However, it is difficult in clinical studies to link p53 mutation status to cancer treatment and clinical outcome, suggesting that the p53 pathway is not fully understood. We have recently reported that the human p53 gene expresses not only 1 but 12 different p53 proteins (isoforms) due to alternative splicing, alternative initiation of translation, and alternative promoter usage.

p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients.

Introduction: Normal function of the p53 network is lost in most cancers, often through p53 mutation. The clinical impact of p53 mutations in breast cancer remains uncertain, especially where p53 isoforms may modify the effects of these p53 mutations.

Methods: Expression of p53β and p53γ isoforms, the isoforms identified in normal breast tissue, was detected by reverse transcription polymerase chain reaction from a cohort of 127 primary breast tumours.

The isoforms of the p53 protein.

p53 is a transcription factor with a key role in the maintenance of genetic stability and therefore preventing cancer formation. It belongs to a family of genes composed of p53, p63, and p73. The p63 and p73 genes have a dual gene structure with an internal promoter in intron-3 and together with alternative splicing, can express 6 and 29 mRNA variants, respectively.

Fibroblast growth factor 1 induced during myogenesis by a transcription-translation coupling mechanism.

Fibroblast growth factor 1 (FGF1) is involved in muscle development and regeneration. The FGF1 gene contains four tissue-specific promoters allowing synthesis of four transcripts with distinct leader regions. Two of these transcripts contain internal ribosome entry sites (IRESs), which are RNA elements allowing mRNA translation to occur in conditions of blockade of the classical cap-dependent mechanism.