Full Text:   <4317>

CLC number: R563.9

On-line Access: 2012-11-05

Received: 2011-12-22

Revision Accepted: 2012-05-30

Crosschecked: 2012-09-07

Cited: 8

Clicked: 7634

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2012 Vol.13 No.11 P.855-866

http://doi.org/10.1631/jzus.B1100382


Nkx2-1: a novel tumor biomarker of lung cancer


Author(s):  Li Yang, Min Lin, Wen-jing Ruan, Liang-liang Dong, En-guo Chen, Xiao-hong Wu, Ke-jing Ying

Affiliation(s):  Department of Respiratory Medicine, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China; more

Corresponding email(s):   hzforest_yang@163.com, ykjsrrsh@163.com

Key Words:  Nkx2-1, TTF-1, Lung cancer, Biomarker, Diagnosis, Prognosis, Therapy


Share this article to: More |Next Article >>>

Li Yang, Min Lin, Wen-jing Ruan, Liang-liang Dong, En-guo Chen, Xiao-hong Wu, Ke-jing Ying. Nkx2-1: a novel tumor biomarker of lung cancer[J]. Journal of Zhejiang University Science B, 2012, 13(11): 855-866.

@article{title="Nkx2-1: a novel tumor biomarker of lung cancer",
author="Li Yang, Min Lin, Wen-jing Ruan, Liang-liang Dong, En-guo Chen, Xiao-hong Wu, Ke-jing Ying",
journal="Journal of Zhejiang University Science B",
volume="13",
number="11",
pages="855-866",
year="2012",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1100382"
}

%0 Journal Article
%T Nkx2-1: a novel tumor biomarker of lung cancer
%A Li Yang
%A Min Lin
%A Wen-jing Ruan
%A Liang-liang Dong
%A En-guo Chen
%A Xiao-hong Wu
%A Ke-jing Ying
%J Journal of Zhejiang University SCIENCE B
%V 13
%N 11
%P 855-866
%@ 1673-1581
%D 2012
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1100382

TY - JOUR
T1 - Nkx2-1: a novel tumor biomarker of lung cancer
A1 - Li Yang
A1 - Min Lin
A1 - Wen-jing Ruan
A1 - Liang-liang Dong
A1 - En-guo Chen
A1 - Xiao-hong Wu
A1 - Ke-jing Ying
J0 - Journal of Zhejiang University Science B
VL - 13
IS - 11
SP - 855
EP - 866
%@ 1673-1581
Y1 - 2012
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1100382


Abstract: 
Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor-1), is a tissue-specific transcription factor of the thyroid, lung, and ventral forebrain. While it has been shown to play a critical role in lung development and lung cancer differentiation and morphogenesis, molecular mechanisms mediating Nkx2-1 cell- and tissue-specific expression in normal and cancerous lungs have yet to be fully elucidated. The recent identification of prognostic biomarkers in lung cancer, particularly in lung adenocarcinoma (ADC), and the different reactivity of patients to chemotherapeutic drugs have opened new avenues for evaluating patient survival and the development of novel effective therapeutic strategies. The function of Nkx2-1 as a proto-oncogene was recently characterized and the gene is implicated as a contributory factor in lung cancer development. In this review, we summarize the role of this transcription factor in the development, diagnosis, and prognosis of lung cancer in the hope of providing insights into the utility of Nkx2-1 as a novel biomarker of lung cancer.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Agoff, S.N., Lamps, L.W., Philip, A.T., Amin, M.B., Schmidt, R.A., True, L.D., Folpe, A.L., 2000. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonarry neuroendocrine tumors. Mod. Pathol., 13(3):238-242.

[2]Au, N.H., Cheang, M., Huntsman, D.G., Yorida, E., Coldman, A., Elliott, W.M., Bebb, G., Flint, J., English, J., Gilks, C.B., et al., 2004. Evaluation if immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. J. Pathol., 204(1):101-109.

[3]Bachurski, C.J., Yang, G.H., Currier, T.A., Gronostajski, R.M., Hong, D., 2003. Nuclear factor I/thyroid transcription factor 1 interactions modulate surfactant protein C transcription. Mol. Cell. Biol., 23(24):9014-9024.

[4]Bai, X.Y., Shen, H., 2008. Mutational analysis of thyroid transcription factor-1 gene (TTF-1) in lung carcinomas. In. Vitro. Cell. Dev. Bio. Anim., 44(1-2):17-25.

[5]Barletta, J.A., Perner, S., Iafrate, A.J., Yeap, B.Y., Weir, B.A., Johnson, L.A., Johnson, B.E., Meyerson, M., Rubin, M.A., Travis, W.D., et al., 2009. Clinical significance of TTF-1 protein expression and TTF-1 gene amplification in lung adenocarcinoma. J. Cell. Mol. Med., 13(8b):1977-1986.

[6]Barlési, F., Pinot, D., Legoffic, A., Doddoli, C., Chetaille, B., Torre, J.P., Astoul, P., 2005. Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung. Br. J. Cancer, 93(4):450-452.

[7]Bejarano, P.A., Baughman, R.P., Biddinger, P.W., Miller, M.A., Fenoglio-Preiser, C., Al Kafaji, B., di Lauro, R., Whitsett, J.A., 1995. Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. Mod. Pathol., 9(4):445-452.

[8]Berghmans, T., Paesmans, M., Mascaux, C., Martin, B., Meert, A.P., Haller, A., Lafitte, J.J., Sculier, J.P., 2006. Thyroid transcription factor 1—a new prognostic factor in lung cancer: a meta-analysis. Ann. Oncol., 17(11):1673-1676.

[9]Besnard, V., Xu, Y., Whitsett, J.A., 2007. Sterol response element binding protein and thyroid transcription factor-1 (Nkx2.1) regulate Abca3 gene expression. Am. J. Physiol. Lung Cell. Mol. Physiol., 293(6):L1395-L1405.

[10]Bingle, C.D., 1997. Thyroid transcription factor-1. Int. J. Biochem. Cell Biol., 29(12):1471-1473.

[11]Bobos, M., Hytiroglou, P., Kostopoulos, I., Karkavelas, G., Papadimitriou, C.S., 2006. Immunohistochemical distinction between Merkel cell carcinoma and small cell carcinoma of the lung. Am. J. Dermatopathol., 28(2):99-104.

[12]Bohinski, R.J., di Lauro, R., Whitsett, J.A., 1994. The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis. Mol. Cell. Biol., 14(9):5671-5681.

[13]Bohinski, R.J., Bejarano, P.A., Balko, G., Warnick, R.E., Whitset, J.A., 1998. Determination of lung as the primary site of cerebral metastatic adenocarcinomas using monoclonal antibody to thyroid transcription factor-1. J. Neuro-oncol., 40(3):227-231.

[14]Bruno, M.D., Bohinski, R.J., Huelsman, K.M., Whitsett, J.A., Korfhagen, T.R., 1995. Lung cell-specific expression of the murine surfactant protein A (SP-A) gene is mediated by interactions between the SP-A promoter and thyroid transcription factor-1. J. Biol. Chem., 270(12):6531-6536.

[15]Cheuk, W., Kwan, M.Y., Suster, S., Chan, J.K., 2001. Immunostaining for thyroid transcription factor-1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch. Pathol. Lab. Med., 125(2):228-231.

[16]Civitareale, D., Lonigro, R., Sinclair, A.J., di Lauro, R., 1989. A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter. EMBO J., 8(9):2537-2542.

[17]Coleman, M.P., Forman, D., Bryant, H., Butler, J., Rachet, B., Maringe, C., Nur, U., Tracey, E., Coory, M., Hatcher, J., et al., 2011. Cancer survival in Australin, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the international Cancer Benchmarking Partnership): an analysis of population-based cancer registry date. Lancet, 377(9760):127-138.

[18]Dave, V., Childs, T., Whitsett, J.A., 2004. Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells. J. Biol. Chem., 279(33):34578-34588.

[19]Devriendt, K., Vanhole, C., Matthijs, G., de Zegher, F., 1998. Deletion of thyroid transcription factor-1 gene in an infant with neonatal thyroid dysfunction and respiratory failure. N. Engl. J. Med., 338(18):1317-1318.

[20]di Loreto, C., di Lauro, V., Puglisi, F., Damante, G., Fabbro, D., Betrami, C.A., 1997. Immunocytochemical expression of tissue-specific transcription factor-1 in lung carcinoma. J. Clin. Pathol., 50(1):30-32.

[21]di Loreto, C., Puglisi, F., di Lauro, V., Damante, G., Beltrami, C.A., 1998. TTF-1 protein expression in pleural malignant mesotheliomas and adenocarcinomas of the lung. Cancer Lett., 124(1):73-78.

[22]Doyle, D.A., Gonzalez, I., Thomas, B., Scavina, M., 2004. Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1. J. Pediatr., 145(2):190-193.

[23]Fabbro, D., di Loreto, C., Stamerra, O., Beltrami, C.A., Lonigro, R., Damante, G., 1996. TTF-1 gene expression in human lung tumors. Eur. J. Cancer, 32(3):512-517.

[24]Fujita, J., Ohtsuki, Y., Bandoh, S., Ueda, Y., Kubo, A., Tojo, Y., Yamaji, Y., Ishida, T., 2003. Expression of thyroid transcription factor-1 in 16 human lung cancer cell lines. Lung Cancer, 39(1):31-36.

[25]Gomez-Fernandez, C., Jorda, M., Delgado, P.I., Ganjei-Azar, P., 2002. Thyroid transcription factor 1: a marker for lung adenocarcinoma in body cavity fluids. Cancer, 96(5):289-293.

[26]Grasberger, H., Ringkananont, U., Lefrancois, P., Abramowicz, M., Vassart, G., Refetoff, S., 2005. Thyroid transcription factor 1 rescues PAX8/p300 synergism impaired by a natural PAX8 paired domain mutation with dominant negative activity. Mol. Endocrinol., 19(7):1779-1791.

[27]Hamdan, H., Liu, H., Li, C., Jones, C., Lee, M., de Lemos, R., Minoo, P., 1998. Structure of the human Nkx2.1 gene. Biochim. Biophy. Acta, 1396(3):336-348.

[28]Haque, A.K., Syed, S., Lele, S.M., Freeman, D.H., Adegboyega, P.A., 2002. Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: strong thyroid transcription factor-1 expression predicts better survival. Appl. Immunohistochem. Mol. Morphol., 10(2):103-109.

[29]Harlamert, H.A., Mira, J., Bejarano, P.A., Baughman, R.P., Miller, M.A., Whitsett, J.A., Yassin, R., 1998. Thyroid transcription factor-1 cytokeratins 7 and 20 in pulmonary and breast carcinomas. Acta Cytol., 42(6):1382-1388.

[30]Harris, T., Pan, Q., Sironi, J., Lutz, D., Tian, J., Sapkar, J., Perez-Soler, R., Keller, S., Locker, J., 2011. Both gene amplification and allelic loss occur at 14q13.3 in lung cancer. Clin. Cancer Res., 17(4):690-699.

[31]Hiramatsu, M., Ninomiya, H., Inamura, K., Nomura, K., Takeuchi, K., Satoh, Y., Okumura, S., Nakagawa, K., Yamori, T., Matsuura, M., et al., 2010. Activation status of receptors tyrosine kinase downstream pathways in primary lung adenocarcinoma with reference of KRAS and EGFR mutations. Lung Cancer, 70(1):94-102.

[32]Holzinger, A., Dingle, S., Bejarano, P.A., Miller, M.A., Weaver, T.E., di Lauro, R., Whitsett, J.A., 1996. Monoclonal antibody to thyroid transcription factor-1: production, characterization, and usefulness in tumor diagnosis. Hybridoma, 15(1):49-53.

[33]Hsu, D.S., Acharya, C.R., Balakumaran, B.S., Riedel, R.F., Kim, M.K., Stevenson, M., Tuchman, S., Mukherjee, S., Barry, W., Dressman, H.K., et al., 2009. Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer. PNAS, 106(13):5312-5317.

[34]Ikeda, K., Clark, J.C., Shaw-White, J.R., Stahlman, M.T., Boutell, C.J., Whitsett, J.A., 1995. Gene structure and expression of human thyroid transcription factor-1 in respiratory epithelial cells. J. Biol. Chem., 270(14):8108-8114.

[35]Islam, K.N., Mendelson, C.R., 2006. Permissive effects of oxygen on cyclic AMP and interleukin-1 stimulation of surfactant protein A gene expression are mediated by epigenetic mechanisms. Mol. Cell. Biol., 26(8):2901-2912.

[36]Iwatani, N., Mabe, H., Devriendt, K., Kodama, M., Miike, T., 2000. Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure. J. Pediatr., 137(2):272-276.

[37]Jiang, B., Wu, G.P., Zhao, Y.J., Wang, S.C., 2008. Transcription expression and clinical significance of TTF-1 mRNA in pleural effusion of patients with lung cancer. Diagn. Cytopathol., 36(12):849-854.

[38]Kaufmann, O., Dietel, M., 2000. Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinoma and large cell carcinoma compared to surfactant proteins A and B. Histopathplogy, 36(1):8-16.

[39]Kelly, S.E., Bachurski, C.J., Burhans, M.S., Glasser, S.W., 1996. Transcription of the lung-specific surfactant protein C gene is mediated by thyroid transcription factor 1. J. Biol. Chem., 271(12):6881-6888.

[40]Kendall, J, Liu, Q., Bakleh, A., Krasnitz, A., Nguyen, K.C., Lakshmi, B., Gerald, W.L., Powers, S., Mu, D., 2007. Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer. PNAS, 104(42):16663-16668.

[41]Khoor, A., Byrd-Gloster, A.L., Nicosia, S.V., 2011. Expression of thyroid transcription factor-1 in malignant pleural effusions. Pathol. Oncol. Res., 17(2):263-267.

[42]Kimura, S., Hara, Y., Pineau, T., Fernandez-Salguero, P., Fox, C.H., Ward, J.M., Gonzalez, F.J., 1996. The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, pituitary. Genes. Dev., 10(1):60-69.

[43]Kolla, V., Gonzales, L.W., Gonzales, J., Wang, P., Angampalli, S., Feinstein, S.I., Ballard, P.L., 2006. Thyroid transcription factors in differentiating type II cells: regulation, isoforms, and target genes. Am. J. Respir. Cell. Mol. Biol., 36(2):213-225.

[44]Krude, H., Schutz, B., Biebermann, H., von Moers, A., Schnabel, D., Neitzel, H., Tonnies, H., Weise, D., Lafferty, A., Schwarz, S., et al., 2002. Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J. Clin. Invest., 109(4):475-480.

[45]Kwei, K.A., Kim, Y.H., Girard, L., Kao, J., Pacyna-Gengelbach, M., Salari, K., Lee, J., Choi, Y.L., Sato, M., Wang, P., et al., 2008. Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer. Oncogene, 27(25):3635-3640.

[46]Li, C., Cai, J., Pan, Q., Minoo, P., 2000. Two functionally distinct forms of Nkx2.1 protein are expressed in the pulmonary epithelium. Biochem. Biophys. Res. Commun., 270(2):462-468.

[47]Li, C., Zhu, N.L., Tan, R.C., Ballard, P.L., Derynck, R., Minoo, P., 2002. Transforming growth factor-β inhibits pulmonary surfactant protein B gene transcription through SMAD3 interactions with NKX2.1 and HNF-3 transcription factors. J. Biol. Chem., 277(41):38399-38408.

[48]Lin, S., Perl, A.K., Shannon, J.M., 2006. Erm/thyroid transcription factor 1 interactions modulate surfactant protein C transcription. J. Biol. Chem., 281(24):16716-16726.

[49]Lin, X., Saad, R.S., Luckasevic, T.M., Silverman, J.F., Liu, Y., 2007. Diagnostic value of CDX-2 and TTF-1 expression in separating metastatic neuroendocrine neoplasms of unknown origin. Appl. Immunohistochem. Mol. Morphol., 15(4):407-414.

[50]Liu, C., Glasser, S.W., Wan, H., Whitsett, J.A., 2002. GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression. J. Biol. Chem., 277(6):4519-4525.

[51]Lotan, T.L., Ye, H., Melamed, J., Wu, X.R., Shih, IeM., Epstein, J.I., 2009. Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma. Am. J. Surg. Pathol., 33(7):1037-1041.

[52]Maeda, Y., Hunter, T.C., Loudy, D.E., Dave, V., Schreiber, V., Whitsett, J.A., 2006. PARP-2 interacts with TTF-1 and regulates expression of surfactant protein-B. J. Biol. Chem., 281(14):9600-9606.

[53]Maeda, Y., Chen, G., Xu, Y., Haitchi, H.M., Du, L., Keiser, A.R., Howarth, P.H., Davies, D.E., Holgate, S.T., Whitsett, J.A., 2011. Airway epithelial transcription factor NKX2-1 inhibits mucous cell metaplasia and Th2 inflammation. Am. J. Respir. Crit. Care. Med., 184(4):421-429.

[54]Martins, S.J., Takagaki, T.Y., Silva, A.G., Gallo, C.P., Silva, F.B., Capelozzi, V.L., 2009. Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma. Lung Cancer, 64(1):105-109.

[55]Missero, C., Pirro, M.T., Simeone, S., Pischetola, M., di Lauro, R., 2001. The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription. J. Biol. Chem., 276(36):33569-33575.

[56]Myong, N.H., 2003. Thyroid transcription factor-1 (TTF-1) expression in human lung carcinomas: its prognostic implication and relationship with expressions of p53 and Ki-67 proteins. J. Korea Med. Sci., 18(4):494-500.

[57]Nakamura, N., Miyagi, E., Murata, S., Kawaoi, A., Katoh, R., 2002. Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues. Mod. Pathol., 15(10):1058-1067.

[58]Naltner, A., Ghaffari, M., Whitsett, J.A., Yan, C., 2000a. Retinoic acid stimulation of the human surfactant protein B promoter is thyroid transcription factor 1 site-dependent. J. Biol. Chem., 275(1):56-62.

[59]Naltner, A., Wert, S., Whitsett, J.A., Yan, C., 2000b. Temporal/spatial expression of nuclear receptor coactivators in the mouse lung. Am. J. Physiol. Lung Cell. Mol. Physiol., 279(6):L1066-L1074.

[60]Oliveira, A.M., Tazelaar, H.D., Myers, J.L., Erickson, L.A., Lloyd, R.V., 2001. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am. J. Surg. Pathol., 25(6):815-819.

[61]Ordonez, N.G., 2000a. Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. Adv. Anat. Pathol., 7(2):123-127.

[62]Ordonez, N.G., 2000b. Value of thyroid transcription factor-1, E-cadherin, BG8, WT1, and CD44S immunostaining in distinguishing epithelial pleural mesothelioma from pulmonary and nonpulmonary adenocarcinoma. Am. J. Surg. Pathol., 24(4):598-606.

[63]Ordonez, N.G., 2000c. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinoma from other small cell carcinomas. Am. J. Surg. Pathol., 24(9):1217-1223.

[64]Park, K.S., Whitsett, J.A., di Palma, T., Hong, J.H., Yaffe, M.B., Zannini, M., 2004. TAZ interacts with TTF-1 and regulates expression of surfactant protein-C. J. Biol. Chem., 279(17):17384-17390.

[65]Pelosi, G., Fraggetta, F., Pasini, F., Maisonneuve, P., Sonzogni, A., Iannucci, A., Terzi, A., Bresaola, E., Valduga, F., Lupo, C., et al., 2001. Immunoreactivity for thyroid transcription facter-1 in stage I non-small cell carcinomas of the lung. Am. J. Surg. Pathol., 25(3):363-372.

[66]Pohlenz, J., Dumitrescu, A., Zundel, D., Martine, U., Schonberger, W., Koo, E., Weiss, R.E., Cohen, R.N., Kimura, S., Refetoff, S., 2002. Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice. J. Clin. Invest., 109(4):469-473.

[67]Puglisi, F., Barbone, F., Damante, G., Bruckbauer, M., di Lauro, V., Beltrami, C.A., di Loreto, C., 1999. Prognostic value of thyroid transcription factor-1 in primary, resected, non-small cell lung carcinoma. Mod. Pathol., 12(3):318-324.

[68]Saad, R.S., Liu, Y.L., Han, H., Landreneau, R.J., Silverman, J.F., 2004. Prognostic significance of thyroid transcription factor-1 expression in both early-stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung. Hum. Pathol., 35(1):3-7.

[69]Saqi, A., Alexis, D., Remotti, F., Bhagat, G., 2005. Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids. Am. J. Clin. Pathol., 123(3):394-404.

[70]Serls, A.E., Doherty, S., Parvatiyar, P., Wells, J.M., Deutsch, G.H., 2005. Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung. Development, 132(1):35-47.

[71]Shah, L., Walter, K.L., Borczuk, A.C., Kawut, S.M., Sonett, J.R., Gorenstein, L.A., Ginsburg, M.E., Steinglass, K.M., Powell, C.A., 2004. Expression of syndecan-1 and expression of epidermal growth factor receptor are associated with survival in patients with non small cell lung carcinoma. Cancer, 101(7):1632-1638.

[72]Srivastava, A., Hornick, J.L., 2009. Immunohistochemical staining for CDX-2, PDX-1, NESP-55 and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am. J. Surg. Pathol., 33(4):626-632.

[73]Stahlman, M.T., Gray, M.E., Whitsett, J.A., 1996. Expression of thyroid transcription factor-1 (TTF-1) in fetal and neonatal human lung. J. Histochem. Cytochem., 44(7):673-678.

[74]Stenhouse, G., Fyfe, N., King, G., Chapman, A., Kerr, K.M., 2004. Thyroid transcription factor 1 in pulmonary adenocarcinoma. J. Clin. Pathol., 57(4):383-387.

[75]Strickland-Marmol, L.B., Khoor, A., Livingston, S.K., Rojiani, A., 2007. Utility of tissue-specific transcription factors 1 and Cdx2 in determining the primary site of metastatic adenocarcinomas to the brain. Arch. Pathol. Lab. Med., 131(11):1686-1690.

[76]Tan, D., Li, Q., Deeb, G., Ramnath, N., Slocum, H.K., Brooks, J., Cheney, R., Wiseman, S., Anderson, T., Loewen, G., 2003. Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study. Hum. Pathol., 34(6):597-604.

[77]Tanaka, H., Yanagisawa, K., Shinjo, K., Taguchi, A., Maeno, K., Tomida, S., Shimada, Y., Osada, H., Kosaka, T., Matsubara, H., et al., 2007. Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1. Cancer Res., 67(13):6007-6011.

[78]Toonen, R.F., Gowan, S., Bingle, C.D., 1996. The lung enriched transcription factor TTF-1 and the ubiquitously expressed proteins Sp1 and Sp3 interact with elements located in the minimal promoter of the rat Clara cell secretory protein gene. Biochem. J., 316(Pt 2):467-473.

[79]Wang, C.L., Yue, D.S., Zhang, Z.F., Zhan, Z.L., Sun, L.N., 2007. Value of thyroid transcription factor-1 in identification of the prognosis of bronchioloalveolar carcinoma. Zhonghua Yi Xue Za Zhi, 87(33):2350-2354 (in Chinese).

[80]Weidenfeld, J., Shu, W., Zhang, L., Millar, S.E., Morrisey, E.E., 2002. The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium. J. Biol. Chem., 277(23):21061-21070.

[81]Weir, B.A., Woo, M.S., Getz, G., Perner, S., Ding, L., Beroukhim, R., Lin, W.M., Province, M.A., Kraja, A., Johnson, L.A., et al., 2007. Characterizing the cancer genome in lung adenocarcinoma. Nature, 450(7171):893-898.

[82]West, H.L., Crowley, J.J., Vance, R.B., Franklin, W.A., Livingston, R.B., Dakhil, S.R., Giguere, J.K., Rivkin, S.E., Kraut, M., Chansky, K., et al., 2005. Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-hour infusion (SWOG 9714): a Southwest Oncology Group study. Ann. Oncol., 16(7):1076-1080.

[83]Winslow, M.M., Dayton, T.L., Verhaak, R.G., Kim-Kiselak, C., Snyder, E.L., Feldser, D.M., Hubbard, D.D., DuPage, M.J., Whittaker, C.A., Hoersch, S., et al., 2011. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature, 473(7345):101-104.

[84]Wislez, M., Antoine, M., Baudrin, L., Poulot, V., Neuville, A., Pradere, M., Longchampt, E., Isaac-Sibille, S., Lebitasy, M.P., Cadranel, J., 2010. Non-mucinomous and mucinous subtypes of adenocarcinoma with bronchioloalveolar carcinoma features differ by biomarker expression and in the response to gefitinib. Lung Cancer, 68(2):185-191.

[85]Yan, C., Naltner, A., Conkright, J., Ghaffari, M., 2001. Protein-protein interaction of retinoic acid receptor α and thyroid transcription factor-1 in respiratory epithelial cells. J. Biol. Chem., 276(24):21686-21691.

[86]Yan, C., Naltner, A., Martin, M., Naltner, M., Fangman, J.M., Gurel, O., 2002. Transcriptional stimulation of the surfactant protein B gene by STAT3 in respiratory epithelial cells. J. Biol. Chem., 277(13):10967-10972.

[87]Yang, L., Yan, D., Bruggeman, M., Du, H., Yan, C., 2004. Mutation of a lysine residue in a homeodomain generatesdominant negative thyroid transcription factor 1. Biochemistry, 43(39):12489-12497.

[88]Yang, M.C., Wang, B., Weissler, J.C., Margraf, L.R., Yang, Y.S., 2003. BR22, a 26 kDa thyroid transcription factor-1 associated protein (TAP26), is expressed in human lung cells. Eur. Respir. J., 22(1):28-34.

[89]Yang, Y.S., Yang, M.C., Wang, B., Weissler, J.C., 2001. BR22, a novel protein, interacts with thyroid transcription factor-1 and activates the human surfactant protein B promoter. Am. J. Respir. Cell. Mol. Biol., 24(1):30-37.

[90]Yatabe, Y., Mitsudomi, T., Takahashi, T., 2002. TTF-1 expression in pulmonary adenocarcinomas. Am. J. Surg. Pathol., 26(6):767-773.

[91]Yi, M., Tong, G.X., Murry, B., Mendelson, C.R., 2002. Role of CBP/p300 and SRC-1 in transcriptional regulation of the pulmonary surfactant protein-A (SP-A) gene by thyroid transcription factor-1 (TTF-1). J. Biol. Chem., 277(4):2997-3005.

[92]Yoon, S.O., Kim, Y.T., Jung, K.C., Jeon, Y.K., Kim, B.H., Kim, C.W., 2011. TTF-1 mRNA-positive circulating tumors cells in the peripheral blood predict poor prognosis in surgically resected non-small cell lung cancer patients. Lung Cancer, 71(2):209-216.

[93]Zhang, P., Han, Y., Huang, L., Li, Q., Ma, D., 2009. Expression and clinical significance of TTF-1 and P63 in NSCLC. Chin. J. Lung Cancer, 12(9):995-999 (in Chinese).

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE