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Somatic acquisition...
Somatic acquisition and signaling of TGFBR1*6A in cancer
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Pasche, Boris (author)
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Knobloch, Thomas J. (author)
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Bian, Yansong (author)
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Liu, Junjian (author)
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Phukan, Sharbani (author)
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Rosman, Diana (author)
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Kaklamani, Virginia (author)
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Baddi, Lisa (author)
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Siddiqui, Farida S (author)
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Frankel, Wendy (author)
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Prior, Thomas W. (author)
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Schuller, David E. (author)
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Agrawal, Amit (author)
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Lang, Jas (author)
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Dolan, M. Eileen (author)
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Vokes, Everett E. (author)
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Lane, William S. (author)
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Huang, Chiang-Ching (author)
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Caldes, Trinidad (author)
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Di Cristofano, Antonio (author)
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Hampel, Heather (author)
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- Nilsson, IngMarie (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- von Heijne, Gunnar (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Fodde, Riccardo (author)
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Murty, V. V. V. S. (author)
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de la Chapelle, Albert (author)
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Weghorst, Christopher M. (author)
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(creator_code:org_t)
- American Medical Association (AMA), 2005
- 2005
- English.
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 294:13, s. 1634-1646
- Related links:
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https://jamanetwork....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Context: TGFBR1*6A is a common polymorphism of the type I transforming growth factor 0 receptor (TGFBR1). Epidemiological studies suggest that TGFBR1*6A may act as a tumor susceptibility allele. How TGFBR1*6A contributes to cancer development is largely unknown.. Objectives: To determine whether TGFBR1*6A is somatically acquired by primary tumors and metastases during cancer development and whether the 3-amino acid deletion that differentiates TGFBR1*6A from TGFBR1 is part of the mature receptor or part of the signal sequence and to investigate TGFBR1*6A signaling in cancer cells. Design, Setting, and Patients: Tumor And germline tissues from 531 patients with a diagnosis of head and neck, colorectal, or breast cancer recruited from 3 centers in the United States and from 1 center in Spain from June 1, 1994, through June 30, 2004, In vitro translation assays, MCF-7 breast cancer cells stably transfected with TGFBR1*6A, TGFBR1, or the vector alone, DLD-1 colorectal cancer cells that endogenously carry TGFBR1*6A, and SW48 colorectal cancer cells that do not carry TGFBR1*6A. Main Outcome Measures: TGFBR1*6A somatic acquisition in cancer. Determination of the amino terminus of the mature TGFBR1*6A and TGFBR1 receptors. Determination of TGF-beta-dependent cell proliferation. Results: TGFBR1*6A was somatically acquired in 13 of 44 (29.5%) colorectal cancer metastases, in 4 of 157 (2.5%) of colorectal tumors, in 4 of 226 (1.8%) head and neck primary tumors, and in none of the 104 patients with breast cancer. TGFBR1*6A somatic acquisition is not associated with loss of heterozygosity, microsatellite instability, or a mutator phenotype. The signal sequences of TGFBR1 and TGFBR1*6A are cleaved at the same site resulting in identical mature receptors. TGFBR1*6A may switch TGF-beta growth inhibitory signals into growth stimulatory signals in MCF-7 breast cancer cells and in DLD-1 colorectal cancer cells. Conclusions: TGFBR1*6A is somatically acquired in 29.5% of liver metastases from colorectal cancer and may bestow cancer cells with a growth advantage in the presence of TGF-beta. The functional consequences of this conversion appear to be mediated by the TGFBR1*6A signal sequence rather than by the mature receptor. The results highlight a new facet of TGF-beta signaling in cancer and suggest that TGFBR1*6A may represent a potential therapeutic target in cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Pasche, Boris
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Knobloch, Thomas ...
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Bian, Yansong
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Liu, Junjian
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Phukan, Sharbani
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Rosman, Diana
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show more...
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Kaklamani, Virgi ...
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Baddi, Lisa
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Siddiqui, Farida ...
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Frankel, Wendy
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Prior, Thomas W.
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Schuller, David ...
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Agrawal, Amit
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Lang, Jas
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Dolan, M. Eileen
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Vokes, Everett E ...
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Lane, William S.
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Huang, Chiang-Ch ...
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Caldes, Trinidad
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Di Cristofano, A ...
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Hampel, Heather
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Nilsson, IngMari ...
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von Heijne, Gunn ...
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Fodde, Riccardo
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Murty, V. V. V. ...
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de la Chapelle, ...
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Weghorst, Christ ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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Stockholm University