Overexpression of p27^BBP in head and neck carcinomas and their lymph node metastases

Abstract

Background. p27 BBP is a regulator of ribosome assembly and an essential nuclear and cytoplasmic component of eukaryotes.Methods. We investigated the immunochemical distribution of p27 BBP in head and neck carcinomas, in the associated normal mucosa, and in regional lymph nodes.Results. p27 BBP is detectable in mucosal cells but is overexpressed in carcinomas, highly concentrated in large polymorphous nucleoli, and even larger and more evident in lymph node metastatic foci. Western blotting confirms increased p27 BBP in carcinomas versus normal mucosa and also in metastatic versus normal lymph nodes. The overexpression of p27 BBP corresponds to mRNA upregulation in carcinomas. Unexpectedly, a 52-kDa band specifically reacting with antibodies to p27 BBP was observed in several carcinomas.Conclusions. p27 BBP alterations are common events in the transition to malignancy and are probably involved in squamous carcinoma progression. Immune reagents raised to p27 BBP may provide additional diagnostic tools for surgical pathology of tumor boundaries and lymph nodes. The 52-kDa band may represent an abnormal form of p27 BBP expressed by transformed airway epithelia.

Eukaryotic initiation factor 6 modulates myofibroblast differentiation at transforming growth factor-β1 transcription level via H2A.Z occupancy and Sp1 recruitment

“…In partial keeping with this observation, eIF6 down-regulation in pre-B-cells reduced the S-phase fraction and increased the G0/G1 fraction, thereby impairing mitotic cycle progression (Miluzio et al, 2011). In accordance with our results, the high eIF6 expression observed in dysplastic carcinomas suggests that eIF6 is involved in the transition to malignancy by impairing the cell's differentiated capacity (Rosso et al, 2004). Thus the partially hindered mitotic cell cycle progression in eIF6 +/− fibroblasts may favor their differentiation into myofibroblasts.…”

“…Moreover, eIF6 overexpression has been reported to cause an aberrant eye development in X. laevis (Miluzio et al, 2011). Furthermore, eIF6 overexpression has been found in selected cancer types, such as colorectal carcinomas (Sanvito et al, 2000), head and neck cancer (Rosso et al, 2004), and malignant mesothelioma (Biffo et al, 1997). It has been proposed that eIF6 is a rate-limiting controller of the initiation of translation, able to affect tumorigenesis and tumor growth (Gandin et al, 2008) and that the impairment of eIF6 activity in cytoplasm restricts lymphomagenesis and tumor progression (Miluzio et al, 2011).…”

eIF6 anti-association activity is required for ribosome biogenesis, translational control and tumor progression

“…In humans, eIF6 was found overexpressed in colon rectal cancer, with peaks in metastatic disease (up to ten-fold) [59], head and neck cancer [54], lung metastasis [36] and acute promyelocytic leukemia [25]. Consistently with the model by which Rack1/PKC complex phosphorylates eIF6, thus promoting 80S joining and activating translation, cancer development is also stimulated by Rack1 and PKCβII.…”

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

“…24,25 The mechanism of eIF6 overexpression may be due to gene amplification. Human eIF6 is mapped to chromosome 20 (20q12), and previous studies [26][27][28][29][30] have identified amplification of the chromosomal region 20q12-13 in ovarian cancer.…”