Parathyroid hormone-related protein serves as a prognostic indicator in oral squamous cell carcinoma.
Parathyroid hormone-related protein serves as a prognostic indicator in oral squamous cell carcinoma.
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DOI：
10.1186/s13046-014-0100-y
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发表时间：
2014-12-18
期刊：
影响因子：
--
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Lv Z;Wu X;Cao W;Shen Z;Wang L;Xie F;Zhang J;Ji T;Yan M;Chen W
我们在前期的研究中，利用基因芯片技术，发现编码甲状旁腺相关蛋白（PTHrP）的甲状旁腺激素样激素（PTHLH）在口腔鳞状细胞癌（OSCC）中表达上调。然而，PTHLH/PTHrP在口腔鳞癌中的功能和预后指标仍不清楚。应用实时荧光定量PCR和免疫印迹法检测9种口腔鳞癌细胞系和36例口腔鳞癌标本中PTHLH的mRNA和蛋白水平。应用小分子干扰RNA（siRNA）技术检测PTHLH/PTHrP在3种口腔鳞癌细胞系中的生物学功能，并应用免疫组化技术检测PTHrP在101例口腔鳞癌和口咽鳞癌患者中的表达。流式细胞仪检测细胞周期，免疫印迹和免疫细胞化学检测细胞周期相关基因。结果表明，9种口腔鳞癌细胞系中PTHLH的mRNA和蛋白水平均明显高于正常口腔黏膜上皮细胞（P < 0.0001）。在36例配对的口腔鳞癌组织中，有32例PTHLH mRNA的表达高于配对的正常切缘组织（P = 0.0001）。结果表明，通过siRNA下调PTHLH/PTHrP表达，可抑制OSCC细胞增殖，抑制平板和软琼脂集落形成，并影响OSCC细胞周期。抗PTHLH siRNA改变了与细胞周期相关的关键蛋白。结果显示，转染抗PTHLH siRNA的细胞中cyclin D1和CDK 4的表达明显降低。另一方面，p21的表达增加。高PTHrP水平与HNSCC病理分化差（P = 0.0001）和预后差（P = 0.0003）有关。本研究提示PTHLH/PTHrP在OSCC中表达上调。因此，PTHLH/PTHrP可能通过影响细胞增殖和细胞周期而参与口腔鳞癌的发病过程，PTHrP蛋白水平可作为判断HNSCC患者预后的指标。
In our previous study, parathyroid hormone-like hormone (PTHLH) which encodes parathyroid hormone-related protein (PTHrP) was revealed to be up-regulated in oral squamous cell carcinoma (OSCC) compared with paired apparently normal surgical margins using microarray method. However, the function and prognostic indicators of PTHLH/PTHrP in OSCC remain obscure. The mRNA levels of PTHLH and its protein levels were investigated in 9 OSCC cell lines and in 36 paired OSCC specimens by real-time PCR and western blotting. The biological function of PTHLH/PTHrP was investigated using small interfering RNA (siRNA) in 3 OSCC cell lines, and immunohistochemistry was used to estimate the prognostic value of PTHrP in 101 patients with head and neck squamous cell carcinoma (HNSCC), including OSCC and oropharyngeal squamous cell carcinoma. Cell cycle was tested by flow cytometry and cell cycle related genes were investigated by western blotting and immunocytochemistry assay. This study showed that the mRNA and protein levels of PTHLH in 9 OSCC cell lines were much higher than that in normal epithelial cells (P < 0.0001). In 36 paired OSCC tissues, PTHLH mRNA expressions were found higher in 32 OSCC tissues than that of paired apparently normal surgical margins (P = 0.0001). The results revealed that the down-regulation of PTHLH/PTHrP by siRNAs could reduce cell proliferation and inhibit plate and soft agar colony formation as well as affect the cell cycle of OSCC cells. The key proteins related to the cell cycle were changed by anti-PTHLH siRNA. The results showed that cyclin D1 and CDK4 expressions were significantly reduced in the cells transfected with anti-PTHLH siRNA. On the other hand, the expression of p21 was increased. The results also showed that high PTHrP level was associated with poor pathologic differentiation (P = 0.0001) and poor prognosis (P = 0.0003) in patients with HNSCC. This study suggests that PTHLH/PTHrP is up-regulated in OSCCs. Therefore, PTHLH/PTHrP could play a role in the pathogenesis of OSCC by affecting cell proliferation and cell cycle, and the protein levels of PTHrP might serve as a prognostic indicator for evaluating patients with HNSCCs.
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DOI：
10.1111/j.1749-6632.1994.tb21767.x
发表时间：
1994-01-01
期刊：
HUMAN ENDOMETRIUM
影响因子：
--
作者：
CASEY, ML;ERK, A;MACDONALD, PC
通讯作者：
MACDONALD, PC
影响因子：
2
作者：
Hoshi, S;Morimoto, T;Okai, T
通讯作者：
Okai, T
影响因子：
6.2
作者：
Deans, C;Wigmore, S;Fearon, KCH
通讯作者：
Fearon, KCH
影响因子：
30.8
作者：
Ghoussaini, Maya;Fletcher, Olivia;Michailidou, Kyriaki;Turnbull, Clare;Schmidt, Marjanka K.;Dicks, Ed;Dennis, Joe;Wang, Qin;Humphreys, Manjeet K.;Luccarini, Craig;Baynes, Caroline;Conroy, Don;Maranian, Melanie;Ahmed, Shahana;Driver, Kristy;Johnson, Nichola;Orr, Nicholas;Silva, Isabel dos Santos;Waisfisz, Quinten;Meijers-Heijboer, Hanne;Uitterlinden, Andre G.;Rivadeneira, Fernando;Hall, Per;Czene, Kamila;Irwanto, Astrid;Liu, Jianjun;Nevanlinna, Heli;Aittomaki, Kristiina;Blomqvist, Carl;Meindl, Alfons;Schmutzler, Rita K.;Mueller-Myhsok, Bertram;Lichtner, Peter;Chang-Claude, Jenny;Hein, Rebecca;Nickels, Stefan;Flesch-Janys, Dieter;Tsimiklis, Helen;Makalic, Enes;Schmidt, Daniel;Bui, Minh;Hopper, John L.;Apicella, Carmel;Park, Daniel J.;Southey, Melissa;Hunter, David J.;Chanock, Stephen J.;Broeks, Annegien;Verhoef, Senno;Hogervorst, Frans B. L.;Fasching, Peter A.;Lux, Michael P.;Beckmann, Matthias W.;Ekici, Arif B.;Sawyer, Elinor;Tomlinson, Ian;Kerin, Michael;Marme, Frederik;Schneeweiss, Andreas;Sohn, Christof;Burwinkel, Barbara;Guenel, Pascal;Truong, Therese;Cordina-Duverger, Emilie;Menegaux, Florence;Bojesen, Stig E.;Nordestgaard, Borge G.;Nielsen, Sune F.;Flyger, Henrik;Milne, Roger L.;Rosario Alonso, M.;Gonzalez-Neira, Anna;Benitez, Javier;Anton-Culver, Hoda;Ziogas, Argyrios;Bernstein, Leslie;Dur, Christina Clarke;Brenner, Hermann;Mueller, Heiko;Arndt, Volker;Stegmaier, Christa;Justenhoven, Christina;Brauch, Hiltrud;Bruening, Thomas;Wang-Gohrke, Shan;Eilber, Ursula;Doerk, Thilo;Schuermann, Peter;Bremer, Michael;Hillemanns, Peter;Bogdanova, Natalia V.;Antonenkova, Natalia N.;Rogov, Yuri I.;Karstens, Johann H.;Bermisheva, Marina;Prokofieva, Darya;Khusnutdinova, Elza;Lindblom, Annika;Margolin, Sara;Mannermaa, Arto;Kataja, Vesa;Kosma, Veli-Matti;Hartikainen, Jaana M.;Lambrechts, Diether;Yesilyurt, Betul T.;Floris, Giuseppe;Leunen, Karin;Manoukian, Siranoush;Bonanni, Bernardo;Fortuzzi, Stefano;Peterlongo, Paolo;Couch, Fergus J.;Wang, Xianshu;Stevens, Kristen;Lee, Adam;Giles, Graham G.;Baglietto, Laura;Severi, Gianluca;McLean, Catriona;Alnaes, Grethe Grenaker;Kristensen, Vessela;Borrensen-Dale, Anne-Lise;John, Esther M.;Miron, Alexander;Winqvist, Robert;Pylkas, Katri;Jukkola-Vuorinen, Arja;Kauppila, Saila;Andrulis, Irene L.;Glendon, Gord;Mulligan, Anna Marie;Devilee, Peter;van Asperen, Christie J.;Tollenaar, Rob A. E. M.;Seynaeve, Caroline;Figueroa, Jonine D.;Garcia-Closas, Montserrat;Brinton, Louise;Lissowska, Jolanta;Hooning, Maartje J.;Hollestelle, Antoinette;Oldenburg, Rogier A.;van den Ouweland, Ans M. W.;Cox, Angela;Reed, Malcolm W. R.;Shah, Mitul;Jakubowska, Ania;Lubinski, Jan;Jaworska, Katarzyna;Durda, Katarzyna;Jones, Michael;Schoemaker, Minouk;Ashworth, Alan;Swerdlow, Anthony;Beesley, Jonathan;Chen, Xiaoqing;Muir, Kenneth R.;Lophatananon, Artitaya;Rattanamongkongul, Suthee;Chaiwerawattana, Arkom;Kang, Daehee;Yoo, Keun-Young;Noh, Dong-Young;Shen, Chen-Yang;Yu, Jyh-Cherng;Wu, Pei-Ei;Hsiung, Chia-Ni;Perkins, Annie;Swann, Ruth;Velentzis, Louiza;Eccles, Diana M.;Tapper, Will J.;Gerty, Susan M.;Graham, Nikki J.;Ponder, Bruce A. J.;Chenevix-Trench, Georgia;Pharoah, Paul D. P.;Lathrop, Mark;Dunning, Alison M.;Rahman, Nazneen;Peto, Julian;Easton, Douglas F.
通讯作者：
Easton, Douglas F.
影响因子：
8.3
作者：
Martín-Ventura, JL;Ortego, M;Egido, JS
通讯作者：
Egido, JS