WordNet

to put down by force or authority; "suppress a nascent uprising"; "stamp down on littering"; "conquer ones desires" (同)stamp down, inhibit, subdue, conquer, curb
reduce the incidence or severity of or stop; "suppress a yawn"; "this drug can suppress the hemorrhage"
put out of ones consciousness (同)repress
an electrical device for suppressing unwanted currents (同)suppresser
someone who suppresses; "dictators are suppressors of free speech" (同)suppresser
a gene that suppresses the phenotypic expression of another gene (especially of a mutant gene) (同)suppresser, suppressor_gene, suppresser gene
(genetics) a segment of DNA that is involved in producing a polypeptide chain; it can include regions preceding and following the coding DNA as well as introns between the exons; it is considered a unit of heredity; "genes were formerly called factors" (同)cistron, factor
an abnormal new mass of tissue that serves no purpose (同)tumour, neoplasm
informal term for information; "give me the gen on your new line of computers"

PrepTutorEJDIC

〈反乱など〉‘を'『鎮圧する』…,‘の'活動を押える / 〈感情・欲望など〉‘を'『抑制する』,抑える / …‘の'発表を禁止する,伏せる
抑圧する人,鎮圧者 / (ラジオ・テレビの)妨害電波(混信)防止装置
遺伝子

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/23 21:45:25」(JST)

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A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.

Two-hit hypothesis

Models of tumour suppression

Unlike oncogenes, tumor suppressor genes generally follow the "two-hit hypothesis", which implies that both alleles that code for a particular protein must be affected before an effect is manifested. This is because if only one allele for the gene is damaged, the second can still produce the correct protein. In other words, mutant tumor suppressors alleles are usually recessive whereas mutant oncogene alleles are typically dominant. The two-hit hypothesis was first proposed by A.G. Knudson for cases of retinoblastoma.^[1] Knudson observed that the age of onset of retinoblastoma followed 2nd order kinetics, implying that two independent genetic events were necessary. He recognized that this was consistent with a recessive mutation involving a single gene, but requiring biallelic mutation. Oncogene mutations, in contrast, generally involve a single allele because they are gain-of-function mutations. There are exceptions to the "two-hit" rule for tumor suppressors, such as certain mutations in the p53 gene product. p53 mutations can function as a "dominant negative", meaning that a mutated p53 protein can prevent the function of normal protein from the un-mutated allele.^[2] Other tumor-suppressor genes that are exceptions to the "two-hit" rule are those that exhibit haploinsufficiency for example PTCH in medulloblastoma. An example of this is the p27Kip1 cell-cycle inhibitor, in which mutation of a single allele causes increased carcinogen susceptibility.^[3]

Functions

Tumor-suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes do both. The functions of tumor-suppressor proteins fall into several categories including the following:^[4]

Repression of genes that are essential for the continuing of the cell cycle. If these genes are not expressed, the cell cycle does not continue, effectively inhibiting cell division.
Coupling the cell cycle to DNA damage. As long as there is damaged DNA in the cell, it should not divide. If the damage can be repaired, the cell cycle can continue.
If the damage cannot be repaired, the cell should initiate apoptosis (programmed cell death) to remove the threat it poses for the greater good of the organism.
Some proteins involved in cell adhesion prevent tumor cells from dispersing, block loss of contact inhibition, and inhibit metastasis. These proteins are known as metastasis suppressors.^[5]^[6]
DNA repair proteins are usually classified as tumor suppressors as well, as mutations in their genes increase the risk of cancer, for example mutations in HNPCC, MEN1 and BRCA. Furthermore, increased mutation rate from decreased DNA repair leads to increased inactivation of other tumor suppressors and activation of oncogenes.^[7]

Examples

The first tumor-suppressor protein discovered was the Retinoblastoma protein (pRb) in human retinoblastoma; however, recent evidence has also implicated pRb as a tumor-survival factor.

Another important tumor suppressor is the p53 tumor-suppressor protein encoded by the TP53 gene. Homozygous loss of p53 is found in 70% of colon cancers, 30–50% of breast cancers, and 50% of lung cancers. Mutated p53 is also involved in the pathophysiology of leukemias, lymphomas, sarcomas, and neurogenic tumors. Abnormalities of the p53 gene can be inherited in Li-Fraumeni syndrome (LFS), which increases the risk of developing various types of cancers.

PTEN acts by opposing the action of PI3K, which is essential for anti-apoptotic, pro-tumorogenic Akt activation.

Other examples of tumor suppressors include VHL, APC, CD95, ST5, YPEL3, ST7, and ST14.

References

^ Knudson AG (1971). "Mutation and Cancer: Statistical Study of Retinoblastoma". Proc Natl Acad of Sci 68 (4): 820–3. doi:10.1073/pnas.68.4.820. PMC 389051. PMID 5279523. //www.ncbi.nlm.nih.gov/pmc/articles/PMC389051/.
^ Baker SJ, Markowitz S, Fearon ER, Willson JK, Vogelstein B. (1990). "Suppression of human colorectal carcinoma cell growth by wild-type p53". Science 249 (4971): 912–5. doi:10.1126/science.2144057. PMID 2144057.
^ Fero ML, Randel E, Gurley KE, Roberts JM, Kemp CJ (1998). "The murine gene p27Kip1 is haplo-insufficient for tumour suppression". Nature 396 (6707): 177–80. doi:10.1038/24179. PMID 9823898.
^ Sherr CJ (January 2004). "Principles of tumor suppression". Cell 116 (2): 235–46. doi:10.1016/S0092-8674(03)01075-4. PMID 14744434.
^ Yoshida BA, Sokoloff MM, Welch DR, Rinker-Schaeffer CW (November 2000). "Metastasis-suppressor genes: a review and perspective on an emerging field". J. Natl. Cancer Inst. 92 (21): 1717–30. doi:10.1093/jnci/92.21.1717. PMID 11058615.
^ Hirohashi S, Kanai Y (2003). "Cell adhesion system and human cancer morphogenesis". Cancer Sci 94 (7): 575–81. doi:10.1111/j.1349-7006.2003.tb01485.x. PMID 12841864.
^ Markowitz S (November 2000). "DNA repair defects inactivate tumor suppressor genes and induce hereditary and sporadic colon cancers". J. Clin. Oncol. 18 (21 Suppl): 75S–80S. PMID 11060332.

External links

TCF21 gene discovery at Ohio State University
Drosophila Oncogenes and Tumor Suppressors - The Interactive Fly
Online book: Tumor Suppressor Genes, published in 2012

UpToDate Contents

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1. 大腸癌の分子遺伝学 molecular genetics of colorectal cancer
2. 甲状腺結節および非髄様甲状腺癌におけるオンコジーンおよび腫瘍抑制遺伝子 oncogenes and tumor suppressor genes in thyroid nodules and nonmedullary thyroid cancer
3. 前立腺癌の分子生物学 molecular biology of prostate cancer
4. 頭頸部の扁平上皮癌化：分子学的および遺伝学的変化 head and neck squamous cell carcinogenesis molecular and genetic alterations
5. 急性骨髄性白血病の分子遺伝学 molecular genetics of acute myeloid leukemia

English Journal

IKBB tumor suppressive role in nasopharyngeal carcinoma via NF-κB-mediated signalling.

Phoon YP1, Cheung AK1,2, Cheung FM3,4, Chan KF5, Wong S6, Wong BW1, Tung SY3,7, Yau CC3,8, Ng WT3,9, Lung ML1,2,3.
International journal of cancer. Journal international du cancer.Int J Cancer.2016 Jan 1;138(1):160-70. doi: 10.1002/ijc.29702. Epub 2015 Aug 10.
Tumor suppressor genes (TSGs) play a prominent role in cancer and are important in the development of nasopharyngeal carcinoma (NPC), which is endemic in Southern China as well as Southeast Asia. Apart from TSGs, aberrant signalling pathways are also commonly associated with tumor progression. Unsur
PMID 26227166

Histone methylation modifiers in cellular signaling pathways.

Alam H1, Gu B1, Lee MG2,3,4.
Cellular and molecular life sciences : CMLS.Cell Mol Life Sci.2015 Dec;72(23):4577-92. doi: 10.1007/s00018-015-2023-y. Epub 2015 Aug 25.
Histone methyltransferases and demethylases epigenetically regulate gene expression by modifying histone methylation status in numerous cellular processes, including cell differentiation and proliferation. These modifiers also control methylation levels of various non-histone proteins, such as effec
PMID 26305020

Transcriptional dysregulation of the deleted in colorectal carcinoma gene in multiple myeloma and monoclonal gammopathy of undetermined significance.

Nagoshi H1, Taki T2, Chinen Y1, Tatekawa S1, Tsukamoto T1, Maegawa S1, Yamamoto-Sugitani M1, Tsutsumi Y1,3, Kobayashi T1, Matsumoto Y1, Horiike S1, Okuno Y4, Fujiwara S4, Hata H5, Kuroda J1, Taniwaki M1,2.
Genes, chromosomes & cancer.Genes Chromosomes Cancer.2015 Dec;54(12):788-95. doi: 10.1002/gcc.22290. Epub 2015 Sep 22.
The deleted in colorectal carcinoma (DCC) gene at 18q21 encodes a netrin-1 receptor, a tumor suppressor that prevents cell growth. While allele loss or decreased expression of DCC has been associated with the progression of solid tumors and hematologic malignancies, including leukemias and malignant
PMID 26390996

Japanese Journal

Context-dependent activation of Wnt signaling by tumor suppressor RUNX3 in gastric cancer cells

Ju Xiaoli,Ishikawa Tomo-o,Naka Kazuhito,Ito Kosei,Ito Yoshiaki,Oshima Masanobu
Cancer Science 105(4), 418-424, 2014-04
… RUNX3 is a tumor suppressor for a variety of cancers. … Moreover, the ChIP analyses revealed that TCF4, β-catenin and RUNX3 bind the promoter region of the Wnt target genes, Axin2 and c-Myc, and the occupancy of TCF4 and β-catenin in these promoter regions is increased by the RUNX3 expression. …
NAID 120005438970

Context-dependent activation of Wnt signaling by tumor suppressor RUNX3 in gastric cancer cells

Ju Xiaoli,Ishikawa Tomo-o,Naka Kazuhito,Ito Kosei,Ito Yoshiaki,Oshima Masanobu
Cancer Science 105(4), 418-424, 2014-04
… RUNX3 is a tumor suppressor for a variety of cancers. … Moreover, the ChIP analyses revealed that TCF4, β-catenin and RUNX3 bind the promoter region of the Wnt target genes, Axin2 and c-Myc, and the occupancy of TCF4 and β-catenin in these promoter regions is increased by the RUNX3 expression. …
NAID 120005418485

BOB.1-positive Classical Hodgkin's Lymphoma Carries Hypermethylation of Its Promoter as Epigenetic Marker of Gene-silencing Memory

Watanabe Takafumi,Kitazawa Riko,Mizuno Yosuke,Kuwahara Natsumi,Ito Chizu,Sugita Atsuro,Haraguchi Ryuma,Kitazawa Sohei
ACTA HISTOCHEMICA ET CYTOCHEMICA 47(3), 125-131, 2014
… When some tumor-suppressor gene products have lost their biological function, impact or significance of derepression of such genes may be little. …
NAID 130004137836