The c-MYC Protooncogene Expression in Cholesteatoma

Abstract

Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma); their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC gene, and the presence of elevated level c-MYC protein in cholesteatoma. In this study we have compared the expression of c-MYC gene in samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11 adults), 15 epidermoid cysts of the skin (atheromas; head and neck region) and 5 normal skin samples (retroauricular region) using RT-qPCR, providing the first precise measurement of the expression of c-MYC gene in cholesteatoma. We have found significantly elevated c-MYC gene expression in cholesteatoma compared to atheroma and to normal skin samples. There was no significant difference, however, in c-MYC gene expression between cholesteatoma samples of children and adults. The significant difference in c-MYC gene expression level in cholesteatoma compared to that of atheroma implies a more prominent hyperproliferative phenotype which may explain the clinical behavior typical of cholesteatoma.

Low expression of microRNA-125b enhances the expression of STAT3 and contributes to cholesteatoma growth

“…Meanwhile, MiR-125b was shown to be down-regulated in psoriasis and cutaneous squamous cell carcinoma, and its overexpression can suppresses the proliferation of keratinocytes [9][10][11]. Cholesteatoma has the same abnormal proliferation characteristics as malignancies, which has been confirmed by many studies which found that many tumour-related genes and proliferation markers had abnormally high expression in cholesteatoma [26,27]. Similar to psoriasis, cholesteatoma has aberrant proliferation of keratinocytes in an environment full of inflammation.…”

Etiopathogenesis of acquired cholesteatoma: Prominent theories and recent advances in biomolecular research

“…Additionally, the proto‐oncogenes c‐myc and c‐jun have been strongly linked to keratinocyte differentiation and proliferation in cholesteatomas . The c‐myc gene is located on chromosome 8q24.…”

“…The c‐myc gene is located on chromosome 8q24. Previous studies have shown that the aneuploidy of chromosome 8 and copy‐number alterations of the c‐myc gene are associated with the proliferative and aggressive nature of cholesteatomas . Aneusomy of chromosomes 7 and 17 has also been suggested to play a crucial role in cholesteatoma growth and bone destruction …”

Analysis of KRT1, KRT10, KRT19, TP53 and MMP9 expression in pediatric and adult cholesteatoma

“…The study was conducted in compliance with the principles of the Declaration of Helsinki (1964). As it was described previously 26 patients with acquired cholesteatoma comprised of 11 females and 15 males were recruited in the study [ 18 ]. The age of cholesteatoma patients ranged between 4 and 65 years (average: 23.4 years).…”

“…The diagnosis of cholesteatoma in all specimens was confirmed by histopathological examination. Demographic data and a brief clinical history including the age, gender of the patients and surgical parameters of cholesteatoma were described in [ 18 ]. In addition to the 26 cholesteatoma samples, 5 control skin samples from the retroauricular region of healthy individuals were also obtained.…”