Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2010, Vol. 06 ›› Issue (06): 456 -461. doi: 10.3877/cma.j.issn.1673-5250.2010.06.021

Review

Research Progress of Signal Transducer and Activator of Transcription 3 and Gynecological Malignant Tumour

Ka-na WANG, Ya-lan XIN, Jian ZHANG   

  1. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
  • Published:2010-12-01
  • Supported by:
    * Project No. 04JY029-077-2, supported by the Science & Technology Department of Sichuan Province

Signal transducer and activator of transcription (STAT) 3 is an important member of signal transducer and activator of transcription(STATs), which was originally identified as a substrate of the Janus kinase(JAK) in Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. It has been demonstrated to receive growth factors and cytokines or other extracellular stimulation. Activated signal transducer and activator of transcription proteins translocate to the nucleus to regulate expression of genes by binding to specific elements within gene promoters, then to regulate tumor-cell proliferation, differentiation and apoptosis. Abnormal activation of the signal transducer and activator of transcription family members have been found in a large group of human malignant tumors.Researches show that abnormal activation of signal transducer and activator of transcription 3 can inhibit apoptosis, thereby promoting tumor-cell proliferation, invasion and metastasis. Instead, by blocking the way, it could inhibit the tumor-cell proliferation and induce apoptosis of cancer cells. Increasing domestic and foreign evidences demonstrate that JAK-STAT pathway may be involved in the oncogenesis of gynecological malignant tumor.With further researches, signal transducer and activator of transcription 3 may provide clues for early diagnosis and prognosis of gynecological malignant tumor, and may provide a new target for therapy, especially for ovarian cancer drug resistance.

图1 STAT3α基本结构
1 Hoey T, Gruaby MJ. STAT3 as mediation of cytokine-induced response[J]. Adv Immunity, 1998, 71: 145-160.
2 Calo V, Migliavacca M, Bazan V, et al. STAT Proteins: From normal control of ellular events to tumorigenesis[J]. J Cell Physiol, 2003, 197(2): 157-168.
3 Petterino C, Podestà G, Ratto A, et al. Immunohistochemical study of phospho-Stat3-ser727 expression in feline mammary gland tumours[J]. Vet Res Commun, 2007, 31(2): 173-184.
4 Zuyao Ni, Wei Lou, Eddy SL, et al. Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells [J]. Cancer Res, 2003, 60(1): 1225-1228.
5 Lutticken C, Wegenka UM, Yuan J, et al. Association of transcription factor APRF and protein kinase JAK 1 with IL-6 signal transducer gpl30[J]. Science, 1994, 263(5143): 89-92.
6 Suganuma M, Okabe S, Kurusu M, et al. Discrete roles of cytokines, TNF-alpha, IL-1, IL-6 in tumor promotion and cell transformation[J]. Int J Oncol, 2002, 20(1): 131-136.
7 Aziz N, Cherwinski H, McMahon M, et al. Complementation of defective colony-stimulating factor I receptor signaling and mitogenesis by raf and v-Src[J]. Mol Cell Biod, 1999, 19(2): 1101-1115.
8 Quintanilla-Martinez L, Kremer M, Specht K, et al. Analysis of signal transducer and activator of transcription 3 (Stat 3) pathway in multiple myeloma: Stat 3 activation and cyclin D1 dysregulation are mutually exclusive events[J]. Am J Pathol, 2003, 162(5): 1449-1461.
9 Wagner M, Siddiqui MA. Signaling networks regulating cardiac myocytesurvival and death[J]. Curr Opin Investig Drugs, 2009, 10(9): 928-937.
10 Dreyling MH, Bullinger L, Ott G, et al. Alterations of the cyclinD1/P16.pRb pathway in mantle cell lymphoma[J]. Cancer Res, 1997, 57(20): 4608-4614.
11 Aaronson DS, Horvath CM. A road map for those who don't know JAK-STAT[J]. Science, 2003, 29(6): 1653-1655.
12 Burkea WM, Jin X, Lin H, et al. Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells[J]. Oncogene, 2001, 20(55): 7925-7934.
13 Selvendiran K, Koga H, Ueno T, et al. Luteolin promotes degradation in signal transducer and activator of transcription 3 in human hepatoma cells: An implication for the antitumor potential of flavonoids[J]. Cancer Res, 2006, 66(9): 4826-4834.
14 Tomida M, Ohtake H, Yokata T, et al. Stat3 up-regulates expression of nicotinamide N -methyltransferase in human cancer cell[J]. J Cancer Res Clin Oncol, 2008, 134(5): 551-557.
15 Allen D, Kenna PF, Palfi A, et al. Development of strategies for conditional RNA interference[J]. J Gene Med, 2007, 9(4): 287-298.
16 Nishimoto A, Yu Y, Lu Z, et al. A Ras homologue member I directly inhibits signal transducers and activators of transcription 3 translocation and activity in human breast and ovarian cancer cells[J]. Cancer Res, 2005, 65(15): 6701-6710.
17 Pathak AK, Bhutani M, Nair AS, et al. Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells[J]. Mol Cancer Res, 2007, 5(9): 943-955.
18 Kotha A, Sekharam M, Cilenti L, et al. Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein[J]. Mol Cancer Ther, 2006, 5(3): 621-629.
19 Daniel GR, Imelda MU, Gong Y, et al. The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis[J]. Cancer, 2006, 107(11): 2730-2740.
20 Huang M, Page C, Reynolds RK, et al. Constitutive activation of stat 3 oncogene product in human ovarian calinonla cells[J]. Gynecol Oncol, 2000, 79(1): 67-73.
21 Yamamotos, Konishi Z, Kuroda H, et al. Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasms: Cot-relation with clinicopathology and patient survival, and analysis serum VEGF levels[J]. Br J Cancer, 1997, 76(9): 1221-1227.
22 Chen BY, Ye DF, Xie X, et al. Expressions of VEGF/VEGFRs and activation of STATs in ovarian carcinoma[J].China J Oncol, 2005, 27(1): 33-37. [陈冰亚,叶大风,谢幸,等.卵巢上皮癌细胞中VEGF和VEGFRs的表达与STATs的活化[J].中华肿瘤杂志,2005, 27(1): 33-37.]
23 Wei D, Le X, Zheng L, et al. STA3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis[J]. Oncogene, 2003, 22: 319.
24 Silver DL, Naora H, Liu J, et al. Activated signal transducer and activator of transcription (STAT) 3: Localization in focal adhesions and function in ovarian cancer cell motility[J]. Cancer Res, 2004, 64(15): 3550-3558.
25 Page C, Huang M, Jin X, et al. Elevated phosphory1ation of AKT and Stat3 in prostate, breast, and cervical cancer cells[J]. Int J Oncol, 2000, 17(1): 23-28.
26 Chen CL, Hsieh FC, Lieblein JC, et al. STAT3 activation in human endometrial and cervical cancers[J]. Br J Cancer, 2007, 96(4): 591-599.
27 Niu G, Wright KL, Huang M, et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis[J]. Oncogene, 2002, 21(13): 2000-2008.
28 Yang SF, Yuan SS, Yeh YT, et al. Positive association between STAT3 and Ki-67 in cervical intraepithelial neoplasiar[J]. Kaohsiung J Med Sci, 2006, 22(11): 539-546.
29 Takemoto S, Ushijima K, Kawano K, et al. Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma[J]. Br J Cancer, 2009, 101: 967-972.
30 Catalano S, Giordano C, Rizza P, et al. Evidence that leptin through STAT and CREB signaling enhances cyclin D1 expression and promotes human endometrial cancer proliferation[J]. J Cell Physiol, 2009, 18(3): 490-500.
31 Gao J, Tian J, Lv Y, et al. Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells[J]. Cancer Sci, 2009, 100(3): 389-395.
[1] Di Wu, Mingxia Li, Mingyang Wang, Runling Ren, Linlin Gao, Zhifeng Yan, Yuanguang Meng. Clinical observation of da Vinci robotic system in the treatment of elderly patient suffered from gynecological malignant tumor[J]. Chinese Journal of Laparoscopic Surgery(Electronic Edition), 2021, 14(06): 332-337.
[2] Xiaorong Qi, Sijing Chen, Ying Zheng. The advantages and disadvantages of laparoendoscopic single site surgery in the treatment of gynecological malignant tumors[J]. Chinese Journal of Laparoscopic Surgery(Electronic Edition), 2018, 11(06): 370-373.
Viewed
Full text


Abstract