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Roles of Steroid Receptor Coactivator-3 and TTF-1 in Lung Development and Lung Cancer
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  • Journal title : Journal of Life Science
  • Volume 25, Issue 12,  2015, pp.1439-1444
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2015.25.12.1439
 Title & Authors
Roles of Steroid Receptor Coactivator-3 and TTF-1 in Lung Development and Lung Cancer
Kwak, Inseok;
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Steroid receptor coactivators (SRC) are transcriptional coactivators. Among SRCs, SRC-3 is the most studied in relation to different types of tumors. However, the role of SRC-3 in early lung development and lung cancer has not been well studied. The expression profiles of SRC-3 showed that SRC-3 contributed to bronchial and alveolar development in embryonic lung development. SRC-3 was strongly expressed in Clara cells and type II alveolar cells during fetal lung development (E17.5- E18.5), and SRC-3 was expressed in both cell types in the adult lung. TTF-1 was expressed in the lungs of heterozygote SRC-3 mice and Clara cell-specific-CCSP-TAg tumor mice, along with SRC-3 expression. The expression of TTF-1 was localized at transformed Clara cells and multifocal adenocarcinomas in lung cancer mice. However, SRC-3 was not expressed in the multifocal adenocarcinomas, suggesting that SRC-3 might not be involved in the invasiveness of lung cancer. Cotransfection of TTF-1 in Clara cell-specific mtCC cell lines resulted in significant activation of CCSP expression. However, cotransfection of SRC-3 had no significant effects on transient transfection. These in vivo and in vitro results suggest that SRC-3 does not play a significant role in lung tumor progression. In conclusion, SRC-3 is involved in bronchial and alveolar development in fetal and adult lungs, but it does not play an important role in the progression of Clara cell-derived lung cancer.
CCSP;lung cancer;lung development;SRC-3;TTF-1;
 Cited by
Alberg, A. J. and Samet, J. M. 2003. Epidemiology of lung cancer. Chest 123, 21S-49S. crossref(new window)

Anzick, S. L., Kononen, J., Walker, R. L., Azorsa, D. O., Tanner, M. M., Guan, X. Y., Sauter, G., Kallioniemi, O. P., Trent, J. M. and Meltzer, S. 1997. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277, 965-968. crossref(new window)

Bingle, C. D. 1997. Thyroid transcription factor-1. Int. J. Biochem. Cell Biol. 29, 1471-1473. crossref(new window)

DeMayo, F. J., Finegold, M. J., Hansen, T. N., Stanley, L. A., Smith, B. and Bullock, D. W. 1991. Expression of SV40 T antigen under control of rabbit uteroglobin promoter in transgenic mice. Am. J. Physiol. 1261, L70-76.

Glaeser, M., Floetotto, T., Hanstein, B., Beckmann, M. W. and Niederacher, D. 2001. Gene amplification and expression of the steroid receptor coactivator SRC3 (AIB1) in sporadic breast and endometrial carcinomas. Horm. Metab. Res. 33, 121-126. crossref(new window)

Gnanapragasam, V. J., Leung, H. Y., Pulimood, A. S., Neal, D. E. and Robson, C. N. 2001. Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer. Br. J. Cancer 85, 1928-1936. crossref(new window)

Hicks, S. M., Vassallo, J. D., Dieter, M. Z., Lewis, C. L., Whiteley, L. O., Fix, A. S. and Lehman-McKeeman, L. D. 2003. Immunohistochemical analysis of Clara cell secretory protein expression in a transgenic model of mouse lung carcinogenesis. Toxicology 187, 217-228. crossref(new window)

Hong, K. U., Reynolds, S. D., Giangreco, A., Hurley, C. M. and Stripp, B. R. 2001. Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am. J. Respir. Cell Mol. Biol. 24, 671-681. crossref(new window)

Iwase, H., Omoto, Y., Toyama, T., Yamashita, H., Hara, Y., Sugiura, H. and Zhang, Z. 2003. Clinical significance of AIB1 expression in human breast cancer. Breast Cancer Res. Treat. 80, 339-345. crossref(new window)

Jemal, A., Murray, T., Samuels, A., Ghafoor, A., Ward, E. and Thun, M. J. 2003. Cancer statistics, CA. Cancer J. Clin. 53, 5-26. crossref(new window)

Kauffman, S. L., Alexander, L. and Sass, L. 1979. Histologicand ultrastructural features of the clara cell adenoma of the mouse lung. Lab. Invest. 40, 708-716.

Kwak, I. S. 2012. Roles of the Steroid Receptor Coactivator-3in Lung Cancer. Cancer Prev. Res. 17, 344-349.

Kwak, I. S, Tsai, S. Y. and DeMayo, F. J. 2004. Genetically engineered mouse models for lung cancer. Annu. Rev. Physiol. 66, 647-663. crossref(new window)

Margraf, L. R., Finegold, M. J., Stanley, L. A., Major, A., Hawkins, H. K. and DeMayo, F. J. 1993. Cloning and tissue-specific expression of the cDNA for the mouse Clara cell 10 kD protein: comparison of endogenous expression to rabbit uteroglobin promoter-driven transgene expression. Am. J. Respir. Cell Mol. Biol. 9, 231-238.

Nord, M., Cassel, T. N., Braun, H. and Suske, G. 2000. Regulation of the Clara cell secretory protein/uteroglobin promoter in lung. Ann. N. Y. Acad. Sci. 923, 154-165.

O’Malley, B. W. 2007. Coregulators: from whence came these “master genes”. Mol. Endocrinol. 21, 1009-1013. crossref(new window)

Ray, M. K., Chen, C. Y., Schwartz, R. J. and DeMayo, F. J. 1996. Transcriptional regulation of a mouse Clara cell-specific protein (mCC10) gene by the NKx transcription factor family members thyroid transciption factor 1 and cardiac muscle-specific homeobox protein (CSX). Mol. Cell. Biol. 16, 2056-2064. crossref(new window)

Schiller, J. H. 2001. Current standards of care in small-cell and non-small-cell lung cancer. Oncology 61, Suppl. 1, 3-13. crossref(new window)

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

Tan, D., Li, Q., Deeb, G., Ramnath, N., Slocum, H. K., Brooks, J., Cheney, R., Wiseman, S., Anderson, T. and 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, 597-604. crossref(new window)

Xu, J., Liao, L., Ning, G., Yoshida-Komiya, H., Deng, C. and O’Malley, B. W. 2000. The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development. Proc. Natl. Acad. Sci. USA 97, 6379-6384. crossref(new window)

Yi, M., Tong, G. X., Murry, B. and 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, 2997-3005. crossref(new window)

Zemke, A. C., Snyder, J. C., Brockway, B. L., Drake, J. A., Reynolds, S. D., Kaminski, N. and Stripp, B. R. 2009. Molecular staging of epithelial maturation using secretory cell-specific genes as markers. Am. J. Respir. Cell Mol. Biol. 40, 340-348. crossref(new window)

Zhou, L., Lim, L., Costa, R. H. and Whitsett, J. A. 1996. Thyroid transcription factor-1, hepatocyte nuclear factor-3beta, surfactant protein B, C, and Clara cell secretory protein in developing mouse lung. J. Histochem. Cytochem. 44, 1183-1193. crossref(new window)