Abstract
The transforming growth factor β (TGF-β) receptors are an important class of tumor suppressor gene. TGF-β markedly inhibits the growth of many epithelial cell types; whereas in contrast, cancers of many different tissue types are commonly TGF-β resistant (10). Many cancer cell lines are resistant to the growth suppressive effects of TGF-β and display evidence of disruption of TGF-β signal transduction (10,4,10). To date, this resistance appears to often result from mutations in the TGF-β receptors or the smad family of TGF-β signaling proteins (5,11,12,14,16).
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References
Alexandrow, M. and Moses, H. (1995) Transforming growth factor β and cell cycle regulation. Cancer Res. 55, 1452–1457.
Chen, T., Carter, D., Garrigue-Antar, L., and Reiss, M. (1998) Transforming growth factor β type I receptor kinase mutant associated with metastatic breast cancer. Cancer Res. 58, 4805–4810.
Garrigue-Antar, L., Munoz-Antonia, T., Antonia, S., Gesmonde, J., Vellucci, V., and Reiss, M. (1995) Missense mutations of the transforming growth factor β type II receptor in human head and neck squamous carcinoma cells. Cancer Res. 55, 3982–3987.
Grady, W., Myeroff, L., Swinler, S., Rajput, A., Thiagalingam, S., Lutterbaugh, J., et al. (1999) Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers. Cancer Res. 59, 320–324.
Hahn, S., Schutte, M., Shamsul Hoque, A., Moskaluk, C., da Costa, L., Rozen-blum, E., et al. (1996) DPC4, a candidate tumor supressor gene at human chromosome 18q21.1. Science 271, 350–353.
Hirai, R. and Fujita, T. (1996) A human transforming growth factor-β type II receptor that contains an insertion in the extracellular domain. Exp. Cell Res. 223, 135–141.
Knaus, P., Lindemann, D., DeCoteau, J., Perman, R., Yankelev, H., Hille, M., et al. (1996) A dominant inhibitory mutant of the type II transforming growth factor P receptor in the malignant progression of a cutaneous T-cell lymphoma. Mol. Cell. Biol. 16, 3480–3489.
Lu, S.-L., Zhang, W.-C., Akiyama, Y., Nomizu, T., and Yuasa, Y. (1996) Genomic structure of the transforming growth factor β type II receptor gene and its mutations in hereditary nonpolyposis colorectal cancers. Cancer Res. 56, 4595–4598.
Lynch, M., Nakashima, R., Song, H., DeGroff, V., Wang, D., Enomoto, T. and Weghorst, C. (1998) Mutational analysis of the transforming growth factor β receptor type II gene in human ovarian carcinoma. Cancer Res. 58, 4227–4232.
Markowitz, S. and Roberts, A. (1996) Tumor supressor activity of the TGF-β pathway in human cancers. Cytokine Growth Factor Rev. 7, 93–102.
Markowitz, S., Wang, J., Myeroff, L., Parsons, R., Sun, L., Lutterbaugh, J., et al. (1995) Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 268, 1336–1338.
Myeroff, L., Parsons, R., Kim, S.-J., Hedrick, L., Cho, K., Orth, K., et al. (1995) A transforming growth factor β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Res. 55, 5545–5547.
Nikawa, J. (1994) A cDNA encoding the human transforming growth factor β receptor suppresses the growth defect of a yeast mutant. Gene 149, 367–372.
Parsons, R., Myeroff, L., Liu, B., Willson, J., Markowitz, S., Kinzler, K., and Vogelstein, B. (1995) Microsatellite instability and mutations of the transforming growth factor β type II receptor gene in colorectal cancer. Cancer Res. 55, 5548–5550. 111
Pasche, B., Luo, Y., Rao, P., Nimer, S., Dmitrovsky, E., Caron, P., et al. (1998) Type I transforming growth factor β receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyadenine tract. Cancer Res. 58, 2727–2732.
Schutte, M., Hruban, R., Hedrick, L., Cho, K., Nadasdy, G., Weinstein, C., et al. (1996) DPC4 gene in various tumor types. Cancer Res. 56, 2527–2530.
Takenoshita, S., Tani, M., Nagashima, M., Hagiwara, K., Bennet, W., Yokota, J., and Harris, C. (1997) Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and intron primers. Oncogene 14, 1255–1258.
Togo, G., Toda, N., Kanai, F., Kato, N., Shiratori, Y., Kishi, K., et al. (1996) A transforming growth factor β type II receptor gene mutation common in sporadic cecum cancer with micro satellite instability. Cancer Res. 56, 5620–5623.
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Grady, W.M., Myeroff, L.L., He, H., Markowitz, S. (2001). Mutation Detection inTGF-β Receptors. In: M., S. (eds) Colorectal Cancer. Methods in Molecular Medicine, vol 50. Humana Press. https://doi.org/10.1385/1-59259-084-5:99
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DOI: https://doi.org/10.1385/1-59259-084-5:99
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