1.
Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system.
Wilfinger, J, Seuter, S, Tuomainen, TP, Virtanen, JK, Voutilainen, S, Nurmi, T, de Mello, VD, Uusitupa, M, Carlberg, C
The Journal of nutritional biochemistry. 2014;(8):875-84
Abstract
Vitamin D(3) belongs to the few nutritional compounds that has, via the binding of its metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to the transcription factor vitamin D receptor (VDR), a direct effect on gene regulation. The relation of thousands of genomic VDR-binding sites to a few hundred primary 1,25(OH)(2)D(3) target genes is still largely unresolved. We studied chromatin domains containing genes for the adhesion molecules CD97 and LRRC8A, the glucose transporter SLC37A2 and the coactivator NRIP1. These domains vary significantly in size (7.3 to 956 kb) but contain each one major VDR-binding site. In monocytic cells these four sites are associated with open chromatin and occupied by VDR, while in macrophage-like cells only the sites of LRRC8A, SLC37A2 and NRIP1 are accessible and receptor bound. The VDR site of CD97 does, in contrast to the three other loci, not carry any DR3-type binding sequence. CD97, LRRC8A, SLC37A2 and NRIP1 are early responding 1,25(OH)(2)D(3) target genes in monocytic cells, while in macrophage-like cells they respond less and, in part, delayed. In primary human peripheral blood mononuclear cells from 71 prediabetic subjects of a vitamin D(3) intervention study (VitDmet) CD97, LRRC8A, SLC37A2 and NRIP1 can be used as transcriptomic biomarkers for classifying human individuals for their possible benefit from vitamin D(3) supplementation. In particular, NRIP1 exceeds the potential of the previously identified marker CD14 by more than 40% and seems to be a well-suited molecular marker for the vitamin D(3) status in the hematopoietic system.
2.
The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the diagnosis of primary and secondary lung carcinomas.
Al-Zahrani, IH
Saudi medical journal. 2008;(7):957-61
Abstract
OBJECTIVE To study the value of immunohistochemical staining of thyroid transcription factor-1 TTF-1, cytokeratin 7 CK7, and cytokeratin 20 CK20 in the differentiation between primary and secondary pulmonary carcinomas. METHODS Forty-three cases of lung carcinoma, 14 squamous cell carcinoma, 12 adenocarcinoma, 8 small cell carcinoma, 3 mesothelioma, and 6 metastatic tumors, were collected from the files of the Pathology Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia between 2004 and 2006. All cases were stained immunohistochemically following Avidin biotin method using monoclonal antibodies to TTF-1, CK7, and CK20. RESULTS Immunohistochemical staining of 43 cases of lung carcinoma revealed nuclear immunoreactivity for TTF-1 in all primary adenocarcinoma, and small cell carcinoma, while cases of squamous cell carcinoma were negative. Mesotheliomas were negative to TTF-1, CK7, and CK20. Metastatic tumors except for one case metastatic from the thyroid gland were negative to TTF-1. Cytokeratin 7 was positively expressed in primary tumors of lung, as well as metastatic tumors from the thyroid and breast. Cytokeratin 20 was negative in all primary lung tumors, while positive in metastatic carcinomas from the colon. CONCLUSION Thyroid transcription factor-1 is a sensitive marker for diagnosis of primary pulmonary adenocarcinoma, and differentiation between poorly differentiated squamous cell carcinoma and small cell carcinoma and adenocarcinoma. Cytokeratin 20 could be a marker for metastatic tumors from the colon to the lung since it was negative in all primary lung tumors.