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Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer
Ist Teil von
Journal of endocrinological investigation, 2015-03, Vol.38 (3), p.313-321
Ort / Verlag
Cham: Springer International Publishing
Erscheinungsjahr
2015
Quelle
MEDLINE
Beschreibungen/Notizen
Objective
The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues.
Materials and methods
Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of
BRAF, NRAS, HRAS
and
KRAS
were also tested.
Results
CYP24A1
mRNA expression was markedly increased in 52 cases (52 %) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level
CYP24A1
in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased
CYP24A1
expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in
CYP27B1
gene expression between neoplastic and normal tissues.
Conclusions
A definite alteration was seen in vitamin D3-inactivating
CYP24A1
gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that
CYP24A1
may also directly be involved in thyroid carcinogenesis.