• Molecules and Cells
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• 제23권2호
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• pp.215-219
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• 2007

In mammals light input resets the central clock of the suprachiasmatic nucleus by inducing secretion of pituitary adenylate cyclase-activating polypeptide (PACAP) from retinal ganglion cells (RGCs). We previously showed that thyroid transcription factor 1 (TTF-1), a homeodomain-containing transcription factor, specifically regulates PACAP gene expression in the rat hypothalamus. In the present study we examined the expression of TTF-1 in PACAP-synthesizing retinal cells. Fluorescence in situ hybridization (FISH) showed that it is abundantly expressed in RGCs of the superior region of the retina, but in only a small subset of RGCs in the inferior region. Double FISH experiments revealed that TTF-1 is exclusively expressed in PACAP-producing RGCs. These results suggest that TTF-1 plays a regulatory role in PACAP-expressing retinal ganglion cells.

• Tuberculosis and Respiratory Diseases
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• 제48권6호
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• pp.879-886
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• 2000

연구배경: 폐특이 전사조절 유전자인 Thyroid Transcription Factor-1 (TTF-1)유전자는 폐에 선택적인 유전자의 표현의 조절에 중요한 전사인자로 작용하고 폐의 발생에서 morphogenic protein으로서 작용한다. 그러나 현재까지 이 TTF-1 유전자의 전사인자에 대한 연구는 거의 미미하다. DNase 1 hypersensitive(DH) regions은 활동적인 염색체에 대한 중요한 표식자이며 유전자를 조절하는 많은 DNA sequences와 밀접한 관계가 있다. 방법 : 추정적인 distal regulatory elements를 밝혀 내기 위해서 TTF-1을 표현하는 인간의 폐선암 세포주인 NCI-H441을 사용해 DNase 1 hypersensitive site assay를 이용하였다. 결과 : TTF-1 유전자에는 전사의 시작부위에서 +150, -450, -800, 그리고 -1500 base pair부위에 4곳의 DH sites가 있음을 할 수 있었다. 결론 : 이상의 결과로 전사 조절부위가 TTF-1 유전자 내에 그리고 5' prime부위에 위치함을 추정할 수 있었다.

• 대한의생명과학회지
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• 제12권3호
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• pp.171-176
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• 2006

Sodium iodide symporter (NIS) plays a key role in thyroid hormone production by efficiently accumulating iodide from the circulating blood into the thyocytes, and this is done against an electrochemical gradient. Thyroid transcription factor-l (TTF-l) is a homeodomain-containing protein expressed in embryonic diencephalons, thyroid, and lung and has been found to bind to thyroid specific promoters and to activate their transcriptional activity. TTF-l may be one of the factors capable of activating NIS gene expression in the thyroid gland, thus it accounts for the lower levels of NIS gene expression that are seen in the extrathyroidal tissues. However, a high frequency of TTF-l expression has been observed, especially in primary lung adenocarcinoma. The present study was undertaken in order to elucidate the relationship between the expression of NIS and TTF-l in primary lung adenocarcinoma. Immunohistochemical studies for NIS and TTF-l were performed in 64 primary lung adenocarcinomas. Immunoreactivities for NIS and TTF-l were found in 49 (76.6%) and 45 (70.3%) out of 64 cases, respectively. Forty-one (83.7%) of the 49 cases with positive NIS immunoreactivity showed positive TTF-l expression, whereas 11 (73.3%) of the 15 cases with negative NIS immunoreactivity showed negative TTF-l expression (P<0.05). So the NIS expression was significantly associated with the TTF-l expression. These findings suggest that TTF-l may be one of the factors capable of activating NIS gene expression in primary lung adenocarcinoma. Further studies are needed to define the relation between NIS and TTF-l for examining the mechanisms of tissue-specific NIS expression.

• Journal of Genetic Medicine
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• 제7권1호
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• pp.9-15
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• 2010

선천성 갑상샘 기능 저하증은 신생아 3,000명 내지 4,000명당 한 명꼴로 발생하며 선천성 내분비 질환 중 가장 흔한 것으로 알려져 있다. 본 질환은 갑상샘 발달 과정의 결함으로 인한 갑상샘 형성 부전 또는 호르몬 합성 장애로 인해 가장 흔히 발생한다. 이는 대부분 산발성으로 발생하나 갑상샘 형성 부전의 2%정도에서 가족성으로 발생하기도 하며 유기화 결함에 의한 갑상샘 기능 저하증은 열성으로 유전된다. 본 질환과 관련된 후보 유전자들은 갑상샘 형성 부전 군과 갑상샘 호르몬 합성 장애 군 등 크게 두 군으로 나뉜다. 갑상샘 형성 부전과 관련된 유전자는 비증후군성에 속하는 것으로 TSHR 유전자가 있고 여러 다른 복합적 기형을 동반한 증후군성에 속하는 것으로 Gsa 유전자 및 갑상샘 전사 인자 유전자(TTF-1, TTF-2, Pax-8) 등이 있다. 호르몬 합성장애와 관련된 것으로 TPO와 TG 유전자가 언급되었고 근래 PDS, NIS와 THOX2 유전자가 소개되었다. 또한 iodothyronine 이동 결함과 관련되어 심각한 신경학적 후유증을 동반할 수 있는 갑상샘 기능 저하증에 대한 유전적 근거가 제시되었다.

• 한국동물위생학회지
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• 제40권2호
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• pp.139-142
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• 2017

A six-year-old male captive nutria (Myocastor coypus) maintained in a closed space with a small vent was found dead in his cage. Gross findings showed multifocal nodules in varying sizes, small 0.5 to large 5 cm in diameter, intermixed with normal parenchyma were scattered all over the surface of the lungs and a kidney, which the cut surface was smooth, compact and whitish in color. Microscopically, small round to oval neoplastic cells with modest to slight amounts of cytoplasm formed acinar and gland-like structures. Immunohistochemically, cells were strongly positive for E-cadherin and slightly reactive for thyroid transcription factor-1 (TTF-1). Based on those diagnostic features, the neoplasia was diagnosed as primary pulmonary adenocarcinoma (small cell type) and metastasized into the kidney. This is the first case report of malignant pulmonary tumor and its metastasis in the nutria.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2987-2991
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• 2015

Background: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (${\leq}60$ vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. Results: A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7 months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed-containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs 5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS. Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were predictors of worse OS. Conclusions: Pemetrexed-containing therapy significantly improved PFS while OS was improved in EGFR mutant patients. Female patients had better PFS and OS. TTF1 expression was not a prognostic marker in advanced non-squamous NSCLC.

• Tuberculosis and Respiratory Diseases
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• 제68권5호
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• pp.290-293
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• 2010

A hidden primary tumor presenting as an isolated lung mass is a diagnostic challenge to physicians because the diagnosis of lung cancer is likely to be made if the histologic findings are not inconsistent with lung cancer. A large lung mass was found incidentally in a 59-year-old man. Although adenocarcinoma was diagnosed by percutaneous needle biopsy, thyroid transcription factor-1 (TTF-1) immunostaining was negative, raising suspicion that there was another primary site. There was no abnormal finding except for the lung mass on a $^{18}FDG$-PET/CT scan and the patient did not complain of any discomfort. Finally, prostatic cancer was confirmed through the study of tumor markers and prostate-specific antigen (PSA) immunostaining. Because of the rare presentation of a single lung mass in malignancies that have another primary site, physicians should carefully review all data before making a final diagnosis of lung cancer.

• 동의생리병리학회지
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• 제23권5호
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• pp.1041-1048
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• 2009

The development of skin metastasis is usually a morbid prognostic feature although they occur infrequently. Adenocarcinomas account for up to about 70% of all metastatic skin cancer. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site because they don't have distinctive histological features. For this reason, immunohistochemistry have been used to help identify the origin of metastatic adenocarcinomas. This study performed immunohistochemical staining with metastatic adenocarcinomas of the skin using a variety of antisera to find out characteristic immunohistochemical findings of them. This study was made upon the 29 cases of metastatic adenocarcinomas of the skin, which had been confirmed histopathologically in Chonbuk National University Hospital from January, 1986 to April, 2006, Paraffin blocks were colledted and homemade tissue arrays were made. We performed immunohistochemical staning using 12 antibodies (MUC1, 2, 5AC, 6, cytokeratin (CK) 7, 20, thyroid transcription factor-1 (TTF-1), estrogen receptor (ER), progesterone receptor (PR), beta-catenin, cox-2, claudin-1). The mean age at the time of diagnosis was 60.7 years and the male to female ratio was 1.2:1.0. The most common primary site was lung, followed by stomach and colorectum. MUC1 was expressed by most colorectal, breast and lung adenocarcinoma. MUC2 was expressed infrequently. MUCSAC was expressed by most gastric and colorectal cancer MUC6 was not specific of any primary site in this series. CK7+/CK20+immunophenotype was observed in gastric, lung, colorectal adenocarcinoma. CK7+/CK20- immunophenotype was observed in breast, lung, endometrial, uterine cervical, bile duct adenocarcinoma, while CK7-/CK20+ immunophenotype was observed only in colorectal adenocarcinoma. This results show the utility of TTF-1 to confirm the pulmonary origin. On the other hand ER and PR were not useful markers to assess the origin of primary tumor in this series.