4_05/2010Cover Picture: Proteomics – Clinical Applications 5/10

When BRCA1 breaks

The most frequent cancer among women, breast cancer arises principally due to mutations in the tumor suppressor genes, BRCA1 and BRCA2/FANCD1. Carriers of BRCA1 mutations have a 50–80% chance of breast cancer by age 70. BRCA1 is highly multi-functional, its most critical function being repair of double-strand breaks in DNA before replication. Other jobs include protein degradation, cell cycle control, transcription regulation, and apoptosis control. A major question is which (if any) of these or other factors are involved in the progression of BRCA1 tumors. Bouley et al. approached the problem using isogenic (+/− Knockdown) strains of HeLa cells, liquid phase IEF and DIGE first and second dimensions, then MALDI-TOF MS to identify proteins significantly shifted in amount. Particularly interesting was the over-expression of replication protein A 1 (RPA1), and RPA2 in HeLaKD cells.

Bouley, J. et al., Proteomics Clin. Appl. 2010, 4, 489–498.

Deconstructing the barrier

Understanding the normal functioning of the human placenta during the course of pregnancy is critical for dealing with the diseases that endanger both mother and fetus. Communication between the two parties occurs primarily through the apical plasma membrane of the syncytiotrophoblast (STB). Here occur exchange of nutrients and gas, transfer of hormones and growth factors, removal of waste, and immunological processing. The membrane is polarized, with the microvillous side in direct contact with maternal blood. Zhang et al. prepared vesicles from the highly enriched membrane fraction, which were analyzed by nano-LC ESI-MS/MS. A total of 296 proteins were identified, some assigned to the placenta for the first time. They found raft domains, markers and anchors; calcium transporters, and signal transduction; a new view of the healthy placenta for future reference.

Zhang, Q. et al., Proteomics Clin. Appl. 2010, 4, 538–549.

Osteosarcoma: spots tell the tale early

Primary osteosarcoma (OS) is one of childhood's most common malignant bone tumors. As a bit of cruel humor, it is separable into two forms — a good responder and a poor responder to chemotherapeutic treatment — after chemo. Surgery plus chemo gave cure rates in the vicinity of 70%, but there were some choices in pretreatment that were best made with foreknowledge of responder type. Kikuta et al. were aware of hints of biomarkers found by others, so they elected to explore with 2-D DIGE. Out of 2250 protein spots, they found 39 that differed depending on the responder status. One of the best markers was peroxiredoxin 2 (PRDX 2), even after the validation by a Western blot on an additional set of four patient samples. It looks promising.

Kikuta, K. et al., Proteomics Clin. Appl. 2010, 4, 560–567.

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