Lymphovascular Invasion in Breast Cancer and p53 Regulators
Disclaimer.The materials on this page are intended for informational and educational purposes. No individuals should use the information, resources or tools contained herein to self-diagnosis or self-treat any health-related condition. The content of the website is not meant to be a substitute for advice provided by a doctor or other qualified health care professional. The company will not be held responsible for any negative consequences arising from the use of information posted on this site.
In 1979, two groups simultaneously reported similar results about the existence of a protein of around 55 kDa that bound to large T antigen in various types of cancerous cells. The p53 protein was named from its protein weighing 53 KDa. The protein was actually regarded as an oncogene at that time, as many tumors produce abundant levels of this protein—a phenomenon that was not observed in normal tissue, and ectopic expression of newly cloned TP53 cDNA was shown to cooperate with oncogenic Ras to transform primary cells in culture. However, it was soon recognized that p53 overexpression could transform cells and promote in vivo tumor growth. This discrepant finding can be attributed to the use of different mutated versions of p53, which originally derived from tumor cells. In 1989, the first murine wild type TP53 cDNA was cloned and it was found that there was an absence of oncogenic activity.
Grade III breast tumors frequently harbor gains at 3q and 5p, and 8q amplifications. More recently, a 19q12 amplification was detected, primarily associated with grade III breast tumors in estrogen-negative samples, which encompasses the CCNE1 gene, among others. Grade I tumors show less complex karyotypes with recurrent gain of 16p, as found in estrogen-positive tumors [Natrajan R, Lambros MB, 2009]. However, to the best of our knowledge, no study has investigated the genomic profile of CNAs related to the presence of LVI in breast carcinomas.
The contribution of TGF-β signaling and the trafficking of integrins and growth factor receptors to mutant p53-driven invasion suggests some interesting new candidates for antimetastatic drug development. However, many questions remain as to how the elements of this pro-invasive program are connected to one another. In particular, we anticipate that the link between p63 and the cell’s migratory and trafficking machinery will provide fertile ground for those interested in targeting the metastatic process.
Natrajan R, Lambros MB, Rodríguez-Pinilla SM, Moreno-Bueno G, Tan DS, Marchió C, et al. Tiling path genomic profiling of grade 3 invasive ductal breast cancers. Clin Cancer Res. 2009;15:2711–22.
Bergamaschi A, Kim YH, Wang P, Sørlie T, Hernandez-Boussard T, Lonning PE, et al. Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosom Cancer. 2006;45:1033–40.
Hirose Y, Sasaki H, Abe M, Hattori N, Adachi K, Nishiyama Y, et al. Subgrouping of gliomas on the basis of genetic profiles. Brain Tumor Pathol. 2013;30:203–8.