Ubiquitin Cytochemical Changes During Azaserine-Initiated Pancreatic Carcinogenesis

Abstract

The ubiquitin (Ub)-proteasome proteolytic system is highly selective, and the specific proteins involved in cell division, growth, activation, signaling and transcription are degraded at different rate depending on the physio-pathological state of the cell. Ubiquitination serves first of all as a signal for protein degradation of short-lived and abnormal proteins under several stressful conditions. The immunocytochemical localization of Ub in some malignant tumours has recently been presented and differences in Ub expression has been observed during malignant transformation. Change in the level of Ub and Ub-conjugated proteins might reflect a higher metabolic-catabolic ratio in neoplastic cells. Most studies have been focused on the malignant stage of tumour progression, and only a few papers have dealt with the change in Ub and Ub-protein conjugates level during the whole progression. To address this problem, we applied an azaserine-induced pancreatic carcinogenesis model, in which premalignant and malignant stages were investigated throughout the progression. The level of Ub immunoreactivity was measured in nucleus and cytoplasm by electron microscopic immunocytochemical and morphometrical methods. We found a significant increase of Ub level in the nucleus and the cytoplasmic area in premalignant atypical acinar cell nodule (AACN) cells and in malignant adenocarcinoma in situ (CIS) cells at month 20 after initiation.

Epigenetic reprogramming in pancreatic premalignancy and clinical implications

“…The expression levels of ubiquitination significantly increase in the nucleus and cytoplasm in premalignant atypical acinar cells and cells of malignant adenocarcinoma in situ ( 129 ). Ring1b catalyzes histone modification H2AK119ub and silences acinar cell transcription factors, which is a key mechanism for triggering acinar cell dedifferentiation and PC development ( 66 ).…”

Adsorption characteristics of nitrogen on activated carbons for sorption compressors

“…Toth isotherm model is a semiempirical equation modified from Langmuir equation, which is utilized for describing the heterogeneous adsorption system and has correct limits at considerable high and very low pressures. The model can be expressed as (Toth, 1971)…”

Characterisation of the progression of azaserine-induced rat pancreatic adenocarcinoma by proliferative cell nuclear antigen, basement membrane laminin and trypsinogen immunohistochemistry

“…Longnecker (1987) was the first to determine its stages based on histological criteria and tumour size. In an effort to render also functional criteria for staging we have carried out followup studies of changes in protein ubiquitinylatedness (Tóth et al 2001), tumour angiogenesis (Nagy et al 2001) and cellular autophagic capacity (RØz et al 1999;Tóth et al 2002). A few of the latter develop into adenocarcinomas (ACs), whose histological substages were termed (Tóth et al 2002) differentiated, anaplastic and invasive ACs.…”