Mutational analysis of the transforming growth factor β receptor type I gene in primary non-small cell lung cancer

Zhang, Hongtao; Fei, Qingyan; Chen, Feng; Qi, Qing-Yuan; Zou, Wei; Wang, Jiucun; Zhang, Rongmei; Tao, Shiheng; Chen, Xiaofeng; Luo, Zewei

doi:10.1016/s0169-5002(03)00121-1

Cited by 27 publications

(42 citation statements)

References 13 publications

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“…The PCR primers used to amplify each of these exons are listed in Table 2. The PCR reaction conditions were described in our previous report (23), except for the annealing temperatures that are listed in Table 2. The DGGE experiment was performed with Dcode Universal Mutation Detection System (Bio-Rad).…”

Section: Methodsmentioning

confidence: 99%

Defective Expression of Transforming Growth Factor β Receptor Type II Is Associated with CpG Methylated Promoter in Primary Non-Small Cell Lung Cancer

Zhang

Chen

Wang

et al. 2004

Clinical Cancer Research

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Section: Methodsmentioning

confidence: 99%

Defective Expression of Transforming Growth Factor β Receptor Type II Is Associated with CpG Methylated Promoter in Primary Non-Small Cell Lung Cancer

Zhang

Chen

Wang

et al. 2004

Clinical Cancer Research

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“…RI*6A, a polymorphic allele of RI, is emerging as a high frequency, low penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies (8). Polymorphisms in the microsatellite region of the RI gene were reported in head and neck cancers as well as non-small cell lung cancer (9,10). Mutations in the kinase domain of the RI gene were associated with metastatic breast cancer (11).…”

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confidence: 99%

Restoration of Transforming Growth Factor-β Signaling through Receptor RI Induction by Histone Deacetylase Activity Inhibition in Breast Cancer Cells

Ammanamanchi

Brattain

2004

Journal of Biological Chemistry

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The loss of transforming growth factor-␤ (TGF-␤) response due to the dysregulation of TGF-␤ receptors type I (RI) and type II (RII) is well known for its contribution to oncogenesis. Estrogen receptor-expressing breast cancer cells are refractory to TGF-␤-mediated growth control because of the reduced expression of TGF-␤ receptors. Although RII is required for the binding of TGF-␤ to RI, RI is responsible for directly transducing TGF-␤ signals through the Smad protein family. Treatment of estrogen receptor-expressing MCF-7L and ZR75 breast cancer cells with the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) led to a dramatic induction of RI. Accumulation of acetylated histones H3 and H4 was observed in the SAHAtreated cells. Chromatin immunoprecipitation analysis followed by PCR with RI promoter-specific primers indicated an accumulation of acetylated histones in chromatin associated with the RI gene, suggesting that histone deacetylation was involved in the transcriptional inactivation of RI. SAHA treatment stimulated RI promoter activity through the inhibition of Sp1/Sp3-associated HDAC activity. Histone acetyltransferase p300 stimulated RI promoter activity, thus further confirming the involvement of HDAC activity in the transcriptional repression of RI. Significantly, SAHA-mediated RI regeneration restored the TGF-␤ response in breast cancer cells.Transforming growth factor-␤ (TGF-␤), 1 a 25-kDa homodimeric polypeptide, plays an important role in the growth inhibition of most normal epithelial and some cancer cells (1). TGF-␤ functions through cell surface receptors referred to as type I (RI) and type II (RII). RI requires RII for the binding of TGF-␤. However, RI is a direct player in the TGF-␤ signaling pathway as it conveys signals from TGF-␤ through the activation of Smad protein family members (2). The loss of TGF-␤ response is well known for its contribution to oncogenesis and tumor progression. Direct involvement of RI in TGF-␤ signal transduction would suggest that loss or reduced expression of RI could contribute to TGF-␤ resistance resulting in a growth advantage that contributes to tumor progression.TGF-␤ resistance due to methylation of the RI promoter or RI promoter repression by Sp1 deficiency was reported to be a cause of TGF-␤ resistance in gastric and colon carcinomas (3,4). The RI gene is frequently mutated in ovarian carcinomas (5). Decreased expression of RI is associated with poor prognosis in bladder transitional cell carcinomas (6). Reduced RI expression is also associated with unfavorable prognosis in esophageal squamous cell carcinoma (7). RI*6A, a polymorphic allele of RI, is emerging as a high frequency, low penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies (8). Polymorphisms in the microsatellite region of the RI gene were reported in head and neck cancers as well as non-small cell lung cancer (9, 10). Mutations in the kinase domain of the RI gene we...

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“…This variant has been reported to be associated with NSCLC, kidney and bladder cancer susceptibility (Zhang et al, 2003;Chen et al, 2004). Patients with invasive and metastatic breast cancer have been reported to have a higher frequency of Int7G24A, and this variant may represent a marker for breast cancer progression (Chen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Growing epidemiological evidence indicates that common variants of the TGF-b pathway receptors that alter TGF-b signalling can modify cancer risk . Two common alleles in the TGFBR1 gene, TGFBR1*6A and Int7G24A, A allele, which reside in exon 1 and intron 7, respectively, have been reported to act as low-penetrance tumour susceptibility alleles (Chen et al, , 2004(Chen et al, , 2006Pasche et al, 1999Pasche et al, , 2004Baxter et al, 2002;Kaklamani et al, 2003;Zhang et al, 2003;Bian et al, 2005;Kaklamani and Pasche, 2005). TGFBR1*6A has a deletion of three alanines within a stretch of nine alanines.…”

mentioning

confidence: 99%

“…Although the functional role of this variant is still to be elucidated, Int7G24A has been found to increase the risk of kidney and bladder cancer and homozygous carriers have more than 3-fold increased risk of developing non-small-cell lung cancer (NSCLC) (Zhang et al, 2003;Chen et al, 2004). A case -control study indicated that this intronic variant allele was significantly more prevalent in invasive and metastatic breast cancer cases and may represent a marker for breast cancer progression (Chen et al, 2006).…”

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TGFBR1*6A and Int7G24A variants of transforming growth factor-β receptor 1 in Swedish familial and sporadic breast cancer

et al. 2007

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Two common variants in transforming growth factor-b receptor 1 (TGFBR1), TGFBR1*6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer. We evaluated the TGFBR1 9A/6A and Int7G24A variant frequencies in two breast cancer cohorts; a population-based cohort of breast cancer with defined family history (n ¼ 459) and in breast cancer patients from a familial cancer clinic (n ¼ 340) and in 856 controls from the Stockholm region. The familial patients from both cohorts were further divided into high-and low-risk familial breast cancer based on pedigree analysis. There was no overall association with either variant and breast cancer risk. The TGFBR1*6A allelic frequency was, however, higher in low-risk familial breast cancer (0.138), compared to controls (0.106; P ¼ 0.04). No significant difference was found in the high-risk familial (0.102) or sporadic cases (0.109; P ¼ 0.83 and 0.83, respectively). TGFBR1*6A carrier status was further associated with a high-grade sporadic breast cancer (odds ratio: 2.27; 95% confidence interval: 1.01 -5.11; P ¼ 0.049). These results indicate that the TGFBR1*6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer. The Int7G24A variant was not associated with breast cancer risk or clinical presentation of the disease including prognosis in our material.

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Mutational analysis of the transforming growth factor β receptor type I gene in primary non-small cell lung cancer

Cited by 27 publications

References 13 publications

Defective Expression of Transforming Growth Factor β Receptor Type II Is Associated with CpG Methylated Promoter in Primary Non-Small Cell Lung Cancer

Defective Expression of Transforming Growth Factor β Receptor Type II Is Associated with CpG Methylated Promoter in Primary Non-Small Cell Lung Cancer

Restoration of Transforming Growth Factor-β Signaling through Receptor RI Induction by Histone Deacetylase Activity Inhibition in Breast Cancer Cells

TGFBR1*6A and Int7G24A variants of transforming growth factor-β receptor 1 in Swedish familial and sporadic breast cancer

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