سایکلین دی۱

CCND1
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	2W96, 2W99, 2W9F, 2W9Z
معین‌کننده‌ها
نام‌های دیگر	CCND1, BCL1, D11S287E, PRAD1, U21B31, cyclin D1
شناسه‌های بیرونی	OMIM: 168461 MGI: 88313 HomoloGene: 1334 GeneCards: CCND1
موقعیت ژن (موش)
کروموزوم	کروموزوم ۷ (موش)
پایان	144,493,662 bp
الگوی گسترش RNA
	; ;
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• protein kinase activity; • GO:0001106 transcription corepressor activity; • transcription factor binding; • histone deacetylase binding; • kinase activity; • cyclin-dependent protein serine/threonine kinase regulator activity; • GO:0001948، GO:0016582 پیوند پروتئینی; • enzyme binding; • proline-rich region binding; • protein kinase binding; • cyclin-dependent protein serine/threonine kinase activity; • GO:0032403 protein-containing complex binding;
ترکیبات سلولی	• سیتوپلاسم; • سیتوزول; • cyclin-dependent protein kinase holoenzyme complex; • membrane; • bicellular tight junction; • transcription repressor complex; • intracellular anatomical structure; • نوکلئوپلاسم; • هسته یاخته;
فرایند زیستی	• cellular response to organic substance; • mammary gland epithelial cell proliferation; • positive regulation of mammary gland epithelial cell proliferation; • response to estradiol; • positive regulation of protein phosphorylation; • Leydig cell differentiation; • GO:0009373 regulation of transcription, DNA-templated; • GO:1904578 response to organic cyclic compound; • response to steroid hormone; • response to corticosterone; • negative regulation of Wnt signaling pathway; • response to magnesium ion; • response to glucocorticoid; • re-entry into mitotic cell cycle; • GO:1901227 negative regulation of transcription by RNA polymerase II; • Wnt signaling pathway; • mammary gland alveolus development; • response to organic substance; • transcription, DNA-templated; • response to vitamin E; • regulation of cell cycle; • response to iron ion; • response to estrogen; • response to calcium ion; • تقسیم یاخته; • cellular response to DNA damage stimulus; • endoplasmic reticulum unfolded protein response; • protein phosphorylation; • regulation of G1/S transition of mitotic cell cycle; • liver regeneration; • mitotic G1 DNA damage checkpoint signaling; • animal organ regeneration; • response to organonitrogen compound; • positive regulation of cell population proliferation; • positive regulation of cyclin-dependent protein serine/threonine kinase activity; • canonical Wnt signaling pathway; • response to UV-A; • چرخه یاخته‌ای; • liver development; • positive regulation of G2/M transition of mitotic cell cycle; • lactation; • response to ethanol; • response to leptin; • negative regulation of epithelial cell differentiation; • fat cell differentiation; • واکنش به اشعه ایکس; • positive regulation of cell cycle; • transcription initiation from RNA polymerase II promoter; • G1/S transition of mitotic cell cycle; • cytokine-mediated signaling pathway; • positive regulation of epithelial cell proliferation; • regulation of cyclin-dependent protein serine/threonine kinase activity; • GO:0007067 رشتمان; • regulation of mitotic nuclear division; • positive regulation of G1/S transition of mitotic cell cycle;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	595
	12443
	ENSG00000110092
	ENSMUSG00000070348
	P24385
	P25322
	NM_053056
	NM_001379248 NM_007631، NM_001379248
	NP_444284
	NP_001366177 NP_031657، NP_001366177
	مشاهده/ویرایش موش

سایکلین دی۱ (انگلیسی: Cyclin D1) یک پروتئین است که در انسان توسط ژن «CCND1» کُدگذاری می‌شود. ژن مذکور بر روی بازوی بلند کروموزوم ۱۱ (باند 11q13) واقع است و در حدود ۱۳٬۳۸۸ جفت باز طول دارد و ۲۹۵ پروتئین را کُدگذاری می‌کند.

اهمیت بالینی

تولید بیش از حد این پروتئین در مراحل آغازین سرطان و پیشرفت تومور مشاهده شده‌است و می‌تواند از طریق رشد بدون حمایت تکیه‌گاه سلولی و همچنین رگ‌سازی وابسته به تولید فاکتور رشد اندوتلیال عروقی، منجر به سرطان‌زایی شود. تولید زیاد این سایکلین دی۱ همچنین سبب کاهش بیان ژنی Fas شده و در نتیجه مقاوت به شیمی‌درمانی پیش می‌آید و سلول‌های سرطانی در برابر آپوپتوز محافظت می‌شوند.

تولید بیش از حد این پروتئین با بقای کمتر بیماران سرطانی و افزایش متاستاز در ارتباط است. چنین افزایشی در میزانِ این پروتئین در سرطان‌های زیر یافت شده‌است:

سرطان ریه از نوع سلول غیر کوچک (۳۰–۴۶٪)
سرطان‌های بافت پوششی سر و گردن (۳۰–۵۰٪)
سرطان لوزالمعده (۲۵٪)
سرطان مثانه (۱۵٪)
آدنوم هیپوفیز (۴۹–۵۴٪)
سرطان پستان(۱۳٪)

بیش‌تولیدی سایکلین دی۱ به‌ویژه در «سرطان‌های پستان نوع ER+» قویاً تأیید شده‌است و عدم تنظیم آن با بروز مقاومت به هورمون‌درمانی در این سرطان‌ها مرتبط است.

جابه‌جایی کروموزومی جایگاه ژنی سایکلین دی۱ در حدود ۱۵ – ۲۰٪ از موارد مولتیپل میلوما یافت شده‌است.

از روش‌های رنگ‌آمیزی ایمونوهیستوشیمی آنتی‌بادی‌های سایکلین دی۱ برای تشخیص لنفوم سلول منتل استفاده می‌شود. همچنین پیشنهاد شده تا از آن به‌عنوان یک نشانگر زیستی برای تشخیص سرطان پستان استفاده شود.

جستارهای وابسته

لنفوم سلول منتل

منابع

↑ GRCm38: Ensembl release 89: ENSMUSG00000070348 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Motokura T, Bloom T, Kim HG, Jüppner H, Ruderman JV, Kronenberg HM, Arnold A (April 1991). "A novel cyclin encoded by a bcl1-linked candidate oncogene". Nature. 350 (6318): 512–5. Bibcode:1991Natur.350..512M. doi:10.1038/350512a0. PMID 1826542.
↑ Lew DJ, Dulić V, Reed SI (September 1991). "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast". Cell. 66 (6): 1197–206. doi:10.1016/0092-8674(91)90042-W. PMID 1833066.
↑ Diehl JA (2002). "Cycling to cancer with cyclin D1". Cancer Biology & Therapy. 1 (3): 226–31. doi:10.4161/cbt.72. PMID 12432268.
↑ Shintani M, Okazaki A, Masuda T, Kawada M, Ishizuka M, Doki Y, Weinstein IB, Imoto M (2002). "Overexpression of cyclin DI contributes to malignant properties of esophageal tumor cells by increasing VEGF production and decreasing Fas expression". Anticancer Research. 22 (2A): 639–47. PMID 12014632.
↑ Jares P, Colomer D, Campo E (October 2007). "Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics". Nature Reviews. Cancer. 7 (10): 750–62. doi:10.1038/nrc2230. PMID 17891190.
↑ Thomas GR, Nadiminti H, Regalado J (December 2005). "Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma". International Journal of Experimental Pathology. 86 (6): 347–63. doi:10.1111/j.0959-9673.2005.00447.x. PMC 2517451. PMID 16309541.
↑ Jin M, Inoue S, Umemura T, Moriya J, Arakawa M, Nagashima K, Kato H (November 2001). "Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II". Lung Cancer. 34 (2): 207–18. doi:10.1016/s0169-5002(01)00225-2. PMID 11679179.
↑ Yamanouchi H, Furihata M, Fujita J, Murakami H, Yoshinouchi T, Takahara J, Ohtsuki Y (January 2001). "Expression of cyclin E and cyclin D1 in non-small cell lung cancers". Lung Cancer. 31 (1): 3–8. doi:10.1016/s0169-5002(00)00160-4. PMID 11162860.
↑ Ikeguchi M, Sakatani T, Ueta T, Kaibara N (September 2001). "Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in esophageal squamous cell carcinoma". Journal of Cancer Research and Clinical Oncology. 127 (9): 531–6. doi:10.1007/s004320100265. PMID 11570573.
↑ Izzo JG, Papadimitrakopoulou VA, Li XQ, Ibarguen H, Lee JS, Ro JY, El-Naggar A, Hong WK, Hittelman WN (November 1998). "Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification". Oncogene. 17 (18): 2313–22. doi:10.1038/sj.onc.1202153. PMID 9811462.
↑ Bartkova J, Lukas J, Müller H, Strauss M, Gusterson B, Bartek J (February 1995). "Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer". Cancer Research. 55 (4): 949–56. PMID 7850812.
↑ Gansauge S, Gansauge F, Ramadani M, Stobbe H, Rau B, Harada N, Beger HG (May 1997). "Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis". Cancer Research. 57 (9): 1634–7. PMID 9134998.
↑ Hall M, Peters G (1996). Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Advances in Cancer Research. Vol. 68. pp. 67–108. doi:10.1016/s0065-230x(08)60352-8. ISBN 9780120066681. PMID 8712071.
↑ Simpson DJ, Frost SJ, Bicknell JE, Broome JC, McNicol AM, Clayton RN, Farrell WE (August 2001). "Aberrant expression of G(1)/S regulators is a frequent event in sporadic pituitary adenomas". Carcinogenesis. 22 (8): 1149–54. doi:10.1093/carcin/22.8.1149. PMID 11470742.
↑ Hibberts NA, Simpson DJ, Bicknell JE, Broome JC, Hoban PR, Clayton RN, Farrell WE (August 1999). "Analysis of cyclin D1 (CCND1) allelic imbalance and overexpression in sporadic human pituitary tumors". Clinical Cancer Research. 5 (8): 2133–9. PMID 10473097.
↑ Barnes DM, Gillett CE (1998). "Cyclin D1 in breast cancer". Breast Cancer Research and Treatment. 52 (1–3): 1–15. doi:10.1023/a:1006103831990. PMID 10066068.
↑ Fantl V, Smith R, Brookes S, Dickson C, Peters G (1993). "Chromosome 11q13 abnormalities in human breast cancer". Cancer Surveys. 18: 77–94. PMID 8013002.
↑ Arnold A, Papanikolaou A (June 2005). "Cyclin D1 in breast cancer pathogenesis". Journal of Clinical Oncology. 23 (18): 4215–24. doi:10.1200/JCO.2005.05.064. PMID 15961768.
↑ Hui R, Finney GL, Carroll JS, Lee CS, Musgrove EA, Sutherland RL (December 2002). "Constitutive overexpression of cyclin D1 but not cyclin E confers acute resistance to antiestrogens in T-47D breast cancer cells". Cancer Research. 62 (23): 6916–23. PMID 12460907.
↑ Hodges LC, Cook JD, Lobenhofer EK, Li L, Bennett L, Bushel PR, Aldaz CM, Afshari CA, Walker CL (February 2003). "Tamoxifen functions as a molecular agonist inducing cell cycle-associated genes in breast cancer cells". Molecular Cancer Research. 1 (4): 300–11. PMID 12612058.
↑ Kenny FS, Hui R, Musgrove EA, Gee JM, Blamey RW, Nicholson RI, Sutherland RL, Robertson JF (August 1999). "Overexpression of cyclin D1 messenger RNA predicts for poor prognosis in estrogen receptor-positive breast cancer". Clinical Cancer Research. 5 (8): 2069–76. PMID 10473088.
↑ Bergsagel PL, Kuehl WM (September 2001). "Chromosome translocations in multiple myeloma". Oncogene. 20 (40): 5611–22. doi:10.1038/sj.onc.1204641. PMID 11607813.
↑ Specht K, Haralambieva E, Bink K, Kremer M, Mandl-Weber S, Koch I, Tomer R, Hofler H, Schuuring E, Kluin PM, Fend F, Quintanilla-Martinez L (August 2004). "Different mechanisms of cyclin D1 overexpression in multiple myeloma revealed by fluorescence in situ hybridization and quantitative analysis of mRNA levels". Blood. 104 (4): 1120–6. doi:10.1182/blood-2003-11-3837. PMID 15090460.
↑ He Y, Liu Z, Qiao C, Xu M, Yu J, Li G (January 2014). "Expression and significance of Wnt signaling components and their target genes in breast carcinoma". Molecular Medicine Reports. 9 (1): 137–43. doi:10.3892/mmr.2013.1774. PMID 24190141.

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[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000070348 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1826542-4] Motokura T, Bloom T, Kim HG, Jüppner H, Ruderman JV, Kronenberg HM, Arnold A (April 1991). "A novel cyclin encoded by a bcl1-linked candidate oncogene". Nature. 350 (6318): 512–5. Bibcode:1991Natur.350..512M. doi:10.1038/350512a0. PMID 1826542.

[pmid1833066-5] Lew DJ, Dulić V, Reed SI (September 1991). "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast". Cell. 66 (6): 1197–206. doi:10.1016/0092-8674(91)90042-W. PMID 1833066.

[Diehl-6] Diehl JA (2002). "Cycling to cancer with cyclin D1". Cancer Biology & Therapy. 1 (3): 226–31. doi:10.4161/cbt.72. PMID 12432268.

[a12014632-7] Shintani M, Okazaki A, Masuda T, Kawada M, Ishizuka M, Doki Y, Weinstein IB, Imoto M (2002). "Overexpression of cyclin DI contributes to malignant properties of esophageal tumor cells by increasing VEGF production and decreasing Fas expression". Anticancer Research. 22 (2A): 639–47. PMID 12014632.

[8] Jares P, Colomer D, Campo E (October 2007). "Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics". Nature Reviews. Cancer. 7 (10): 750–62. doi:10.1038/nrc2230. PMID 17891190.

[9] Thomas GR, Nadiminti H, Regalado J (December 2005). "Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma". International Journal of Experimental Pathology. 86 (6): 347–63. doi:10.1111/j.0959-9673.2005.00447.x. PMC 2517451. PMID 16309541.

[10] Jin M, Inoue S, Umemura T, Moriya J, Arakawa M, Nagashima K, Kato H (November 2001). "Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II". Lung Cancer. 34 (2): 207–18. doi:10.1016/s0169-5002(01)00225-2. PMID 11679179.

[11] Yamanouchi H, Furihata M, Fujita J, Murakami H, Yoshinouchi T, Takahara J, Ohtsuki Y (January 2001). "Expression of cyclin E and cyclin D1 in non-small cell lung cancers". Lung Cancer. 31 (1): 3–8. doi:10.1016/s0169-5002(00)00160-4. PMID 11162860.

[12] Ikeguchi M, Sakatani T, Ueta T, Kaibara N (September 2001). "Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in esophageal squamous cell carcinoma". Journal of Cancer Research and Clinical Oncology. 127 (9): 531–6. doi:10.1007/s004320100265. PMID 11570573.

[13] Izzo JG, Papadimitrakopoulou VA, Li XQ, Ibarguen H, Lee JS, Ro JY, El-Naggar A, Hong WK, Hittelman WN (November 1998). "Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification". Oncogene. 17 (18): 2313–22. doi:10.1038/sj.onc.1202153. PMID 9811462.

[14] Bartkova J, Lukas J, Müller H, Strauss M, Gusterson B, Bartek J (February 1995). "Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer". Cancer Research. 55 (4): 949–56. PMID 7850812.

[15] Gansauge S, Gansauge F, Ramadani M, Stobbe H, Rau B, Harada N, Beger HG (May 1997). "Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis". Cancer Research. 57 (9): 1634–7. PMID 9134998.

[16] Hall M, Peters G (1996). Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Advances in Cancer Research. Vol. 68. pp. 67–108. doi:10.1016/s0065-230x(08)60352-8. ISBN 9780120066681. PMID 8712071.

[17] Simpson DJ, Frost SJ, Bicknell JE, Broome JC, McNicol AM, Clayton RN, Farrell WE (August 2001). "Aberrant expression of G(1)/S regulators is a frequent event in sporadic pituitary adenomas". Carcinogenesis. 22 (8): 1149–54. doi:10.1093/carcin/22.8.1149. PMID 11470742.

[18] Hibberts NA, Simpson DJ, Bicknell JE, Broome JC, Hoban PR, Clayton RN, Farrell WE (August 1999). "Analysis of cyclin D1 (CCND1) allelic imbalance and overexpression in sporadic human pituitary tumors". Clinical Cancer Research. 5 (8): 2133–9. PMID 10473097.

[19] Barnes DM, Gillett CE (1998). "Cyclin D1 in breast cancer". Breast Cancer Research and Treatment. 52 (1–3): 1–15. doi:10.1023/a:1006103831990. PMID 10066068.

[20] Fantl V, Smith R, Brookes S, Dickson C, Peters G (1993). "Chromosome 11q13 abnormalities in human breast cancer". Cancer Surveys. 18: 77–94. PMID 8013002.

[a15961768-21] Arnold A, Papanikolaou A (June 2005). "Cyclin D1 in breast cancer pathogenesis". Journal of Clinical Oncology. 23 (18): 4215–24. doi:10.1200/JCO.2005.05.064. PMID 15961768.

[a12460907-22] Hui R, Finney GL, Carroll JS, Lee CS, Musgrove EA, Sutherland RL (December 2002). "Constitutive overexpression of cyclin D1 but not cyclin E confers acute resistance to antiestrogens in T-47D breast cancer cells". Cancer Research. 62 (23): 6916–23. PMID 12460907.

[23] Hodges LC, Cook JD, Lobenhofer EK, Li L, Bennett L, Bushel PR, Aldaz CM, Afshari CA, Walker CL (February 2003). "Tamoxifen functions as a molecular agonist inducing cell cycle-associated genes in breast cancer cells". Molecular Cancer Research. 1 (4): 300–11. PMID 12612058.

[24] Kenny FS, Hui R, Musgrove EA, Gee JM, Blamey RW, Nicholson RI, Sutherland RL, Robertson JF (August 1999). "Overexpression of cyclin D1 messenger RNA predicts for poor prognosis in estrogen receptor-positive breast cancer". Clinical Cancer Research. 5 (8): 2069–76. PMID 10473088.

[25] Bergsagel PL, Kuehl WM (September 2001). "Chromosome translocations in multiple myeloma". Oncogene. 20 (40): 5611–22. doi:10.1038/sj.onc.1204641. PMID 11607813.

[26] Specht K, Haralambieva E, Bink K, Kremer M, Mandl-Weber S, Koch I, Tomer R, Hofler H, Schuuring E, Kluin PM, Fend F, Quintanilla-Martinez L (August 2004). "Different mechanisms of cyclin D1 overexpression in multiple myeloma revealed by fluorescence in situ hybridization and quantitative analysis of mRNA levels". Blood. 104 (4): 1120–6. doi:10.1182/blood-2003-11-3837. PMID 15090460.

[pmid_=_24190141-27] He Y, Liu Z, Qiao C, Xu M, Yu J, Li G (January 2014). "Expression and significance of Wnt signaling components and their target genes in breast carcinoma". Molecular Medicine Reports. 9 (1): 137–43. doi:10.3892/mmr.2013.1774. PMID 24190141.