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Genetics Group Work - Gene Project: Somatostatin receptor 2

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Working as a group:

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Group Member's Individual Research Topic:

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To do list:

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  • really define somatostatin, receptor, and why it is "2"
    • break down the words (maybe this isn't a good idea??) I just think it would be pretty informative for the reader to have an idea of what words they are reading
  • add links to difficult or confusing words
  • how it is being studied
    • Somatostatin Receptor 2, or SST2, is being studied in by seeing its affect on inhibiting growth hormones and the duplication of cells. [1]
  1. ^ Peverelli, E.; Giardino, E.; Treppiedi, D.; Catalano, R.; Mangili, F.; Locatelli, M.; Lania, A.G.; Arosio, M.; Spada, A. (2017-12-20). "A novel pathway activated by somatostatin receptor type 2 (SST2): Inhibition of pituitary tumor cell migration and invasion through cytoskeleton protein recruitment". International Journal of Cancer. 142 (9): 1842–1852. doi:10.1002/ijc.31205. ISSN 0020-7136. PMID 29226331. S2CID 205957126.

Somatostatin Receptor 2

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Nathan - Introduction:

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The Somatostatin receptor 2 (SSTR2), which belongs to the G-protein coupled receptor family, is a gene that functions at many places in the body, including tumors, but has highest activity in the brain.[1] In humans, SSTR2 activity is observed in the adrenal, brain, kidney, liver, prostate, stomach, spleen and many more body parts.[2] SSTR2 can function as an inhibitor, receptor and even stimulate development to fulfill its purpose.[3] The somatostatin receptor 2 is effective in that it keeps the systems of the body in check. SSTR2 is located on chromosome 17 on the long arm in position 25.1 in humans.[4] This gene can be found in many species but is observed mainly in mammals.[5]This gene functions in many animals including cows, pigs, mice, dogs, guinea pigs, wild yaks, and even some species of fish and amphibians. The SSTR2 gene is extremely useful in many areas and is especially observed in the medical field. SSTR2 is known to be useful for identification and even inhibition of tumors, cancers and other processes that get the body out of balance. Neuroendocrine tumors will over-express the somatostatin receptor 2 to either control the tumor or inhibit tumor growth completely.[6] The expression of somatostatin receptor 2 in found in most tumors.[7] The over-expression of somatostatin receptor 2 allows for greater ability to target certain signals in order to inhibit the tumor growth. SSTR2 is expressed in the central nervous system and pancreas and it also aids in neuroendocrine tumors by assisting to anticipate a reaction to radio-peptide therapy.[8] SSTR2 is also very useful for many imaging studies used in medicine.[8] Somatostatin receptor 2 also has the ability to stimulate apoptosis in many cells including cancer cells.[9] SSTR2 has even been shown to have increased levels in people with certain cancers such as prostate and breast cancer.[10] In this way, the somatostatin receptor 2 is somewhat of a defense system by inhibiting, receiving or stimulating when needed in order to keep the body in the correct condition. Cancer researchers are even looking at the somatostatin receptor 2 gene as a possible treatment in cancer patients because of its ability to inhibit tumor growths.[11] Cancer researchers may look at exploiting the somatostatin receptor in cancer patients once it is determined how the somatostatin receptor interacts with cancer cells differently than with normal cells. The somatostatin receptor 2 is very effective and useful component in the body which may be utilized further in the medical field in the future.

  1. ^ Database, GeneCards Human Gene. "SSTR2 Gene - GeneCards | SSR2 Protein | SSR2 Antibody". www.genecards.org. Retrieved 2018-11-10.
  2. ^ "SSTR2 somatostatin receptor 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-11-10.
  3. ^ "SSTR2 - Somatostatin receptor type 2 - Homo sapiens (Human) - SSTR2 gene & protein". www.uniprot.org. Retrieved 2018-11-10.
  4. ^ "SSTR2 Symbol Report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2018-11-10.
  5. ^ "ortholog_gene_6752[group] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-11-10.
  6. ^ Wang, Yuhong; Wang, Wei; Jin, Kaizhou; Fang, Cheng; Lin, Yuan; Xue, Ling; Feng, Shiting; Zhou, Zhiwei; Shao, Chenghao (2017-3). "Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors". Oncology Letters. 13 (3): 1165–1174. doi:10.3892/ol.2017.5591. ISSN 1792-1074. PMC 5403486. PMID 28454229. {{cite journal}}: Check date values in: |date= (help)
  7. ^ Reubi, Jean; Waser, Beatrice; Schaer, Jean-Claude; Laissue, Jean A. (2001-05-17). "Somatostatin receptor sst1–sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands". European Journal of Nuclear Medicine. 28 (7): 836–846. doi:10.1007/s002590100541. ISSN 0340-6997. PMID 11504080. S2CID 8727308.
  8. ^ a b "SSTR2 - Clinical: Somatostatin Receptor 2 (SSTR2), Immunostain, Technical Component Only". www.mayomedicallaboratories.com. Retrieved 2018-11-10.
  9. ^ Teijeiro, Rosa; Rios, Ramon; Costoya, Jose; Castro, Ramon; Bello, Jose; Devesa, Jesus; Arce, Victor (2002). "Activation of Human Somatostatin Receptor 2 Promotes Apoptosis Through a Mechanism that is Independent from Induction of p53". Cellular Physiology and Biochemistry. 12 (1): 31–38. doi:10.1159/000047824. ISSN 1015-8987. PMID 11914546. S2CID 33281755.
  10. ^ Tiscornia, María Mercedes; González, Heidi Soledad; Lorenzati, María Angélica; Zapata, Pedro Darío (2015-01-30). "Association Between Methylation of SHP-1 Isoform I and SSTR2A Promoter Regions with Breast and Prostate Carcinoma Development". Cancer Investigation. 33 (3): 61–69. doi:10.3109/07357907.2014.1001892. ISSN 0735-7907. PMID 25635370. S2CID 2694433.
  11. ^ Callison, J. Clay; Walker, Ronald C.; Massion, Pierre P. (2011). "Somatostatin Receptors in Lung Cancer: From Function to Molecular Imaging and Therapeutics". Journal of Lung Cancer. 10 (2): 69–76. doi:10.6058/jlc.2011.10.2.69. ISSN 1598-7809. PMC 4319675. PMID 25663834.

Emily - Discovery:

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There is a group of somatostatin receptors called the somatostatin receptor family. All of the members of the somatostatin receptor family are proteins that sit on the surface of the cell membrane and are responsible for the communication between cells [1]. In 1972 [2], scientist were on the trek to discover more information on the hypothalamus and its "release factors." [2]Studies showed patterns of inhibitory activity of the hypothalamus release factors which led scientists in the direction to discover somatostatin, known as the somatropin release-inhibiting factor, or SRIF. We now know that the SRIF is located at 3q28 (long arm of the third chromosome at the twenty-eighth position) in humans [2]. Peering into location 3q28, the majority of proteins code for the pancreas, ovaries, and prostate along with other components of the endocrine system and nervous system [3], so it can be drawn that the receptor family has great influence among these systems. The family was first discovered in a segment of a rat's pituitary gland known as the tumor cell line http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=61[4]. A cell line is grown as a culture under controlled conditions, so the first discovery was found by culturing these cells in controlled conditions and in an environment outside of its norm. There, researchers found that the tumor cell line expresses a cell dividing inhibitor known as the transforming growth factor beta (TGF-beta) [5] and also acts as an inhibitor to the milk producing hormone in female mammals, prolactin, and growth hormones. Researchers studied the activity of the receptors by conducting an assay with Ligand binding studies [6], which basically means they were conducting studies to see how prevalent the binding of the receptors occurred [7][6]. Differences in how prevalently they receptors bonded revealed the existence of multiple receptors [6]. Based on the ligand binding affinity and the receptors' signaling mechanisms, the receptor family was divided into 2 different groups, and within those groups, 5 subgroups. The group with a high affinity binding were classified under the SRIF1 group with sst2, sst3, and sst5 in the subgroup, while the receptors with low affinity binding were classified under the SRIF2 group with sst1 and sst4 in the subgroup. Manipulations with the somatostatin receptors are used for many therapies in both the endocrine and nervous system, and now that we know the groups and subgroups of the receptor family, therapy treatment is much more efficient and effective. For example, as you continue reading the article, you will notice the importance and advancements of oncology and tumor treatments, as well as other ways the somatostatin receptors are working and advancing the world of medicine. [8].

According to https://www.ncbi.nlm.nih.gov/gene/6752 [9], the somatostatin receptor 2 is found on the chromosome 17 (chart below is directly from https://www.ncbi.nlm.nih.gov/gene/6752, copywrite infringement not intended). Information was gathered and determined from a sample of individuals, and conclusions were drawn upon location and other information regarding the SSRT2 protein [9].

Gene: SSTR2
Title: somatostatin receptor 2
Location: 73,165,021..73,171,955
Length: 6,935 nt
[Positional Info]
NC_000017.11 position: 73,168,608
Gene position: 3,588
  1. ^ "The Virtual Cell Textbook - Cell Biology". www.ibiblio.org. Retrieved 2018-11-07.
  2. ^ a b c Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette; Holst, Jens Juul (2003-09-22). "Somatostatin receptors". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1616 (1): 1–84. doi:10.1016/S0005-2736(03)00235-9. ISSN 0005-2736. PMID 14507421.
  3. ^ "Chromosome 3". atlasgeneticsoncology.org. Retrieved 2018-11-09.
  4. ^ http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=61. {{cite web}}: Missing or empty |title= (help)
  5. ^ Yamashita, H.; Okadome, T.; Franzén, P.; ten Dijke, P.; Heldin, C. H.; Miyazono, K. (1995-01-13). "A rat pituitary tumor cell line (GH3) expresses type I and type II receptors and other cell surface binding protein(s) for transforming growth factor-beta". The Journal of Biological Chemistry. 270 (2): 770–774. doi:10.1074/jbc.270.2.770. ISSN 0021-9258. PMID 7822309.
  6. ^ a b c "Somatostatin receptors | Introduction | BPS/IUPHAR Guide to PHARMACOLOGY". www.guidetopharmacology.org. Retrieved 2018-11-09.
  7. ^ "Definition of Assay". MedicineNet. Retrieved 2018-11-09.
  8. ^ "Prolactin | You and Your Hormones from the Society for Endocrinology". www.yourhormones.info. Retrieved 2018-11-07.
  9. ^ a b "SSTR2 somatostatin receptor 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-11-09.

Destiny - :

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Dominque - :

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Nick - Significance :

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The somatostatin hormone itself can negatively affect the uptake of hormones in the body and may play a role in some hormonal conditions. Somatostatin 2 receptors have been found in concentration on the surface of tumor cells, particularly those associated with the neuroendocrine system where the overexpression of somatostatin can lead to many complications. [1][2] Due to this, these receptors are considered a prospective aid for the detection of tumors, especially in patients who present with conditions like hypothyroidism and Cushing’s syndrome. [3][4] A synthetic version of the somatostatin hormone, octreotide, has been successfully used in combination with radio-peptide tracers to locate adrenal gland tumors through scintigraphic imaging. [5] A similar method may be utilized to carry and more accurately administer radioactive treatments to tumors. [4] Octreotide and other analogs are preferred for this use due to their possessing of an extended half life compared to the naturally-occurring hormone allowing for more flexibility when used for such treatments. [4]

The association of somatostatin 2 receptors on tumors has also lead to the suggestion of possible alternatives to current tumor treatment methods. The binding of synthetic somatostatin hormones such as octreotide to receptors has been seen to reduce the production of hormones and is now being considered for use in the treatment of some pituitary tumors. One group suggests that the treatment method would be particularly effective against thyrotropin-secreting pituitary adenomas (TSHomas), though further inquiries and clinical trials are needed.[3]

SSTR2 is also being investigated for its potential use as a reporter gene in for the visualization of regional gene expression. One study tested this by comparing the PET/CT and light imaging results of laboratory rats’ musculature obtained through the use of a human somatostatin receptor 2 vector and a control luciferase vector. [5] The study suggests that somatostatin receptor genes could be an effective substitute for the current viral-based vectors since the sstr genes elicits less of an immune response and has overall been well-tolerated by the trial patients’ bodies. This form of treatment may be especially useful for the study of gene expression in larger mammals whose larger body mass may obstruct clear visualization of deep tissue areas. [5] The use of sstr2 and sstr5 as biomarkers to track the progress of and treat neuroendocrine tumors displaying circulating tumor cells is also being investigated due to these cells’ somatostatin receptor gene expressivity. [6]

References

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  1. ^ "Joint Program in Nuclear Medicine". www.med.harvard.edu. Retrieved 2018-11-10.
  2. ^ Childs, Alexa; Vesely, Clare; Ensell, Leah; Lowe, Helen; Luong, Tu Vinh; Caplin, Martyn E; Toumpanakis, Christos; Thirlwell, Christina; Hartley, John A (2016-12-06). "Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours". British Journal of Cancer. 115 (12): 1540–1547. doi:10.1038/bjc.2016.377. ISSN 0007-0920. PMC 5155369. PMID 27875519.
  3. ^ a b Yu, Benxia; Zhang, Zhongsheng; Song, Hao; Chi, Yuchun; Shi, Chunling; Xu, Miao (2017-04-23). "Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma)". Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 23: 1947–1955. doi:10.12659/MSM.903377. ISSN 1234-1010. PMC 5411020. PMID 28434012.
  4. ^ a b c Dluhy (I), Kennedy(II), Robert G. (I), John W. (II) (August 1998). "The Biology and Clinical Relevance of Somatostatin Receptor Scintigraphy in Adrenal Tumor Management". Yale Journal of Biology and Medicine. 70 (5–6): 565–575. CiteSeerX 10.1.1.278.1040. PMC 2589262. PMID 9825485.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ a b c Hofmann, M.; Gazdhar, A.; Weitzel, T.; Schmid, R.; Krause, T. (2006-12-20). "PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy". Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 569 (2): 509–511. doi:10.1016/j.nima.2006.08.161. ISSN 0168-9002.
  6. ^ Childs, Alexa; Vesely, Clare; Ensell, Leah; Lowe, Helen; Luong, Tu Vinh; Caplin, Martyn E; Toumpanakis, Christos; Thirlwell, Christina; Hartley, John A (2016-12-06). "Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours". British Journal of Cancer. 115 (12): 1540–1547. doi:10.1038/bjc.2016.377. ISSN 0007-0920. PMC 5155369. PMID 27875519.

Dylan - :

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