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）』「2018/02/02 00:12:12」(JST)

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A tumor suppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. The loss of these genes may be even more important than proto-oncogene/oncogene activation for the formation of many kinds of human cancer cells.^[1] Tumor suppressor genes can be grouped into categories including caretaker genes, gatekeeper genes, and landscaper genes; the classification schemes are evolving as medicine advances, learning from fields including molecular biology, genetics, and epigenetics.

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.^[2] 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.^[3]

Other tumor-suppressor genes that are exceptions to the "two-hit" rule are those that exhibit haploinsufficiency, including PTCH in medulloblastoma and NF1 in neurofibroma. An example of this is the p27Kip1 cell-cycle inhibitor, in which mutation of a single allele causes increased carcinogen susceptibility.^[4]

Functions

Tumor-suppressor genes, or more precisely, the proteins for which they code, either have a damping 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:^[5]

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 organisms produced
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.^[6]^[7]
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.^[8]

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 65% 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.

As costs of DNA sequencing have diminished, many cancers have now been sequenced for the first time, revealing novel tumor suppressors. Among the most frequently mutated genes are components of the SWI/SNF chromatin remodeling complex, which are lost in about 20% of tumors.^[9]

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

References

^ Weinberg, Robert A (2014). "The Biology of Cancer." Garland Science, page 231.
^ Knudson AG (1971). "Mutation and Cancer: Statistical Study of Retinoblastoma". Proc Natl Acad Sci USA. 68 (4): 820–3. doi:10.1073/pnas.68.4.820. PMC 389051 . PMID 5279523.
^ 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.
^ Shain, AH; Pollack, JR (2013). "The spectrum of SWI/SNF mutations, ubiquitous in human cancers". PLoS ONE. 8 (1): e55119. doi:10.1371/journal.pone.0055119. PMC 3552954 . PMID 23355908.

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
Tumor Suppressor Gene Database, 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. カウデン症候群などのPTEN過誤腫症候群 pten hamartoma tumor syndrome including cowden syndrome
4. 慢性リンパ性白血病の病態生理および遺伝学的特徴 pathophysiology and genetic features of chronic lymphocytic leukemia
5. 前立腺癌の分子生物学 molecular biology of prostate cancer

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★リンクテーブル★

リンク元	「癌抑制遺伝子」「antioncogene」「がん抑制遺伝子」「cancer suppressor gene」「growth suppressor gene」
拡張検索	「tumor suppressor gene product」
関連記事	「suppress」「suppressor」「tumor suppressor」「tumor」