Protein Expression Analysis in Uterine Cervical Cancer for Potential Targets in Treatment.

Specific markers in lesions of the human uterine cervix cancer (UCC) are still needed for prognostic, diagnostic and/or therapeutic purposes. In this study we evaluated key molecules at protein level between normal epithelium, cervical intraepithelial neoplasia (CIN1-3) and invasive cancer of a group of molecules previously reported at mRNA level. For that purpose, human formalin-fixed paraffin embedded tissue microarrays (TMAs) were constructed containing 205 Mexican tissue core specimens. Immunohistochemistry and quantitative analysis of histological staining was performed against twenty-two distinct proteins for each core and the processing platform ImageJ. In the progression of the disease we found key statistical differences for the proteins SEL1, Notch3 and SOCS3. High expressions of SEL1L, Notch3 and SOCS3 have potential value to increase the prognostic of UCC in combination with markers such as p16INK4a. This study identified key drivers in cervical carcinogenesis that should be evaluated for the development of UCC therapies.

Role for apoptosis-inducing factor in the physiological death of cerebellar neurons.

Apoptosis-inducing factor (AIF) is implicated in caspase-independent apoptotic-like death. AIF released from mitochondria translocates to the nucleus, where it mediates some apoptotic events such as chromatin condensation and DNA degradation. Here, the role of AIF in the neuronal death was studied under physiological conditions. When we analyzed the cellular localization of AIF during cerebellar development, we found a significant increase in the number of neurons with nuclear AIF localization in an age-dependent manner. On the other hand, cerebellar granule neurons (CGN) chronically cultured in low concentration of potassium (5 mM; K5) die with apoptotic-like characteristics after five days. In the present study we found that K5 induces a caspase-dependent apoptotic-like death of CGN as well as a late nuclear translocation of AIF. When CGN death induced by K5 was carried out in the presence of a general inhibitor of caspases, there was a slight decrement of cell death, but neurons eventually died by showing apoptotic-like features such as phosphatidylserine translocation and nuclear condensation. Besides, there was a significant increment of nuclear AIF translocation. These findings support the idea that AIF could be involved in apoptotic-like death of CGN and that it could be an alternative mechanism of neuronal death during cerebellar development.