Expression and In Vitro Functions of the Ghrelin Axis in Endometrial Cancer

Hormones and Cancer

Volumn 1, Issue 5, 2010, Pages 245-255

  Fung, Jenny N T ^a   Seim, Inge ^b   Wang, Dengfeng ^a   Obermair, Andreas ^c   Chopin, Lisa K ^b   Chen, Chen ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

^c Queensland Centre for Gynaecological Cancer   (Australia)

Author keywords

Anti apoptosis; Differentiation; Endometrial cancer; Ghrelin; Growth hormone secretagogue receptor; Proliferation

Indexed keywords

GHRELIN; GHRELIN RECEPTOR; GROWTH HORMONE SECRETAGOGUE RECEPTOR; MESSENGER RNA;

ARTICLE; CANCER CELL; CANCER TISSUE; CELL DEATH; CELL PROLIFERATION; CELL SURVIVAL; ENDOMETRIUM CANCER; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOBLOTTING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REAL TIME POLYMERASE CHAIN REACTION;

ADULT; AGED; AGED, 80 AND OVER; CELL PROLIFERATION; CELL SEPARATION; ENDOMETRIAL NEOPLASMS; FEMALE; GHRELIN; HUMANS; IMMUNOBLOTTING; MIDDLE AGED; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTORS, GHRELIN; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

EID: 78650186098     PISSN: 18688497     EISSN: 18688500     Source Type: Journal    
DOI: 10.1007/s12672-010-0047-1     Document Type: Article

References (63)

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58: 71-96.
2. Kitchener H (2006) Management of endometrial cancer. Eur J Surg Oncol 32: 838-843.
3. Bansal N, Yendluri V, Wenham RM (2009) The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control 16: 8-13.
4. Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M, Nayak N, Genbecev-Krtolica O et al (2007) Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biol Reprod 76: 102-117.
5. Tabibzadeh S (1996) The signals and molecular pathways involved in human menstruation, a unique process of tissue destruction and remodelling. Mol Hum Reprod 2: 77-92.
6. Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Manson JE, Li J, Harris TG et al (2008) A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomark Prev 17: 921-929.
7. Berstein LM, Tchernobrovkina AE, Gamajunova VB, Kovalevskij AJ, Vasilyev DA, Chepik OF, Turkevitch EA et al (2003) Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer. J Cancer Res Clin Oncol 129: 245-249.
8. Ito K, Utsunomiya H, Yaegashi N, Sasano H (2007) Biological roles of estrogen and progesterone in human endometrial carcinoma-new developments in potential endocrine therapy for endometrial cancer. Endocr J 54: 667-679.
9. Schally AV, Varga JL, Engel JB (2008) Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer. Nat Clin Pract Endocrinol Metab 4: 33-43.
10. Zhao L, Yano T, Osuga Y, Nakagawa S, Oishi H, Wada-Hiraike O, Tang X et al (2008) Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone. Int J Oncol 32: 593-601.
11. Tanaka K, Minoura H, Isobe T, Yonaha H, Kawato H, Wang DF, Yoshida T, Kojima M, Kangawa K, Toyoda N (2003) Ghrelin is involved in the decidualization of human endometrial stromal cells. J Clin Endocrinol Metab 88: 2335-2340.
12. Tawadros N, Salamonsen LA, Dimitriadis E, Chen C (2007) Facilitation of decidualization by locally produced ghrelin in the human endometrium. Mol Hum Reprod 13: 483-489.
13. Budak E, Fernandez Sanchez M, Bellver J, Cervero A, Simon C, Pellicer A (2006) Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril 85: 1563-1581.
14. Aghajanova L, Rumman A, Altmae S, Wanggren K, Stavreus-Evers A (2010) Diminished endometrial expression of ghrelin and ghrelin receptor contributes to infertility. Reprod Sci 17: 823-832.
15. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660.
16. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M et al (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273: 974-977.
17. Ghelardoni S, Carnicelli V, Frascarelli S, Ronca-Testoni S, Zucchi R (2006) Ghrelin tissue distribution: comparison between gene and protein expression. J Endocrinol Invest 29: 115-121.
18. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87: 2988.
19. Gualillo O, Caminos J, Blanco M, Garcia-Caballero T, Kojima M, Kangawa K, Dieguez C, Casanueva F (2001) Ghrelin, a novel placental-derived hormone. Endocrinology 142: 788-794.
20. Jeffery PL, Murray RE, Yeh AH, McNamara JF, Duncan RP, Francis GD, Herington AC, Chopin LK (2005) Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocr Relat Cancer 12: 839-850.
21. Gaytan F, Barreiro ML, Caminos JE, Chopin LK, Herington AC, Morales C, Pinilla L et al (2004) Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors. J Clin Endocrinol Metab 89: 400-409.
22. Jeffery PL, Herington AC, Chopin LK (2002) Expression and action of the growth hormone releasing peptide ghrelin and its receptor in prostate cancer cell lines. J Endocrinol 172: R7-R11.
23. Yeh AH, Jeffery PL, Duncan RP, Herington AC, Chopin LK (2005) Ghrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer. Clin Cancer Res 11: 8295-8303.
24. Takahashi K, Furukawa C, Takano A, Ishikawa N, Kato T, Hayama S, Suzuki C et al (2006) The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer. Cancer Res 66: 9408-9419.
25. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25: 402-408.
26. Abramoff MD, Magelhaes PJ, Ram SJ (2004) Image processing with ImageJ. Biophoton Int 11: 36-42.
27. Li S, Zhou Y, Wang R, Zhang H, Dong Y, Ip C (2007) Selenium sensitizes MCF-7 breast cancer cells to doxorubicin-induced apoptosis through modulation of phospho-Akt and its downstream substrates. Mol Cancer Ther 6: 1031-1038.
28. Fister S, Schlotawa L, Gunthert AR, Emons G, Grundker C (2008) Increase of doxorubicin-induced apoptosis after knock-down of gonadotropin-releasing hormone receptor expression in human endometrial, ovarian and breast cancer cells. Gynecol Endocrinol 24: 24-29.
29. Wan X, Li J, Xie X, Lu W (2007) PTEN augments doxorubicin-induced apoptosis in PTEN-null Ishikawa cells. Int J Gynecol Cancer 17: 808-812.
30. Waseem T, Rehman Javaid Ur F, Ahmad MA, Qureshi MA (2008) Role of ghrelin axis in colorectal cancer: a novel association. Peptides 29: 1369-1376.
31. Dagli AF, Aydin S, Kocdor H, Gurates B, Sahin I, Catak Z, Ozercan MR, Ozercan IH (2010) Ghrelin expression of endometrium hyperplasia and endometrioid carcinoma. Gynecol Endocrinol. doi: 10. 3109/09513590. 2010. 488772.
32. Kuramoto H (1972) Studies of the growth and cytogenetic properties of human endometrial adenocarcinoma in culture and its development into an established line. Acta Obstet Gynaecol Jpn 19: 47-58.
33. Duxbury MS, Waseem T, Ito H, Robinson MK, Zinner MJ, Ashley SW, Whang EE (2003) Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. Biochem Biophys Res Commun 309: 464-468.
34. Delhanty PJ, van Koetsveld PM, Gauna C, van de Zande B, Vitale G, Hofland LJ, van der Lely AJ (2007) Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway. Am J Physiol Endocrinol Metab 293: E302-E309.
35. Murata M, Okimura Y, Iida K, Matsumoto M, Sowa H, Kaji H, Kojima M, Kangawa K, Chihara K (2002) Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem 277: 5667-5674.
36. Wang DH, Hu YS, Du JJ, Hu YY, Zhong WD, Qin WJ (2009) Ghrelin stimulates proliferation of human osteoblastic TE85 cells via NO/cGMP signaling pathway. Endocr 35: 112-117.
37. Kim SW, Her SJ, Park SJ, Kim D, Park KS, Lee HK, Han BH, Kim MS, Shin CS, Kim SY (2005) Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells. Bone 37: 359-369.
38. Maccarinelli G, Sibilia V, Torsello A, Raimondo F, Pitto M, Giustina A, Netti C, Cocchi D (2005) Ghrelin regulates proliferation and differentiation of osteoblastic cells. J Endocrinol 184: 249-256.
39. Guo M, Hay BA (1999) Cell proliferation and apoptosis. Curr Opin Cell Biol 11: 745-752.
40. Konturek PC, Burnat G, Rau T, Hahn EG, Konturek S (2008) Effect of adiponectin and ghrelin on apoptosis of Barrett adenocarcinoma cell line. Dig Dis Sci 53: 597-605.
41. Granata R, Settanni F, Biancone L, Trovato L, Nano R, Bertuzzi F, Destefanis S et al (2007) Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3′, 5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-kinase/Akt signaling. Endocrinology 148: 512-529.
42. Zhao H, Liu G, Wang Q, Ding L, Cai H, Jiang H, Xin Z (2007) Effect of ghrelin on human endothelial cells apoptosis induced by high glucose. Biochem Biophys Res Commun 362: 677-681.
43. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D et al (2002) Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 159: 1029-1037.
44. Granata R, Settanni F, Trovato L, Destefanis S, Gallo D, Martinetti M, Ghigo E, Muccioli G (2006) Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic beta-cells. J Endocrinol Invest 29: RC19-RC22.
45. Zhang Y, Ying B, Shi L, Fan H, Yang D, Xu D, Wei Y et al (2007) Ghrelin inhibit cell apoptosis in pancreatic beta cell line HIT-T15 via mitogen-activated protein kinase/phosphoinositide 3-kinase pathways. Toxicology 237: 194-202.
46. Wang W, Zhang D, Zhao H, Chen Y, Liu Y, Cao C, Han L, Liu G (2010) Ghrelin inhibits cell apoptosis induced by lipotoxicity in pancreatic beta-cell line. Regul Pept 161: 43-50.
47. Kim MS, Yoon CY, Jang PG, Park YJ, Shin CS, Park HS, Ryu JW et al (2004) The mitogenic and antiapoptotic actions of ghrelin in 3T3-L1 adipocytes. Mol Endocrinol 18: 2291-2301.
48. Chung H, Kim E, Lee DH, Seo S, Ju S, Lee D, Kim H, Park S (2007) Ghrelin inhibits apoptosis in hypothalamic neuronal cells during oxygen-glucose deprivation. Endocrinology 148: 148-159.
49. Liu Y, Chen L, Xu X, Vicaut E, Sercombe R (2009) Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2. BMC Physiol 9: 17.
50. Sowers MR, Wildman RP, Mancuso P, Eyvazzadeh AD, Karvonen-Gutierrez CA, Rillamas-Sun E, Jannausch ML (2008) Change in adipocytokines and ghrelin with menopause. Maturitas 59: 149-157.
51. Markowska A, Ziolkowska A, Nowinka K, Malendowicz LK (2009) Elevated blood active ghrelin and normal total ghrelin and obestatin concentrations in uterine leiomyoma. Eur J Gynaecol Oncol 30: 281-284.
52. McKee KK, Palyha OC, Feighner SD, Hreniuk DL, Tan CP, Phillips MS, Smith RG, van der Ploeg LH, Howard AD (1997) Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol Endocrinol 11: 415-423.
53. Cassoni P, Ghe C, Marrocco T, Tarabra E, Allia E, Catapano F, Deghenghi R, Ghigo E, Papotti M, Muccioli G (2004) Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines. Eur J Endocrinol 150: 173-184.
54. Cassoni P, Papotti M, Ghe C, Catapano F, Sapino A, Graziani A, Deghenghi R, Reissmann T, Ghigo E, Muccioli G (2001) Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab 86: 1738-1745.
55. Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ, Ghigo E, van der Lely AJ (2005) Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 90: 1055-1060.
56. Gauna C, Delhanty PJ, van Aken MO, Janssen JA, Themmen AP, Hofland LJ, Culler M, Broglio F, Ghigo E, van der Lely AJ (2006) Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently of the growth hormone secretagogue receptor type 1a and the corticotropin releasing factor 2 receptor. Mol Cell Endocrinol 251: 103-111.
57. Neary NM, Druce MR, Small CJ, Bloom SR (2006) Acylated ghrelin stimulates food intake in the fed and fasted states but desacylated ghrelin has no effect. Gut 55: 135.
58. Thompson NM, Gill DA, Davies R, Loveridge N, Houston PA, Robinson IC, Wells T (2004) Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145: 234-242.
59. Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y et al (2006) Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 147: 2306-2314.
60. Barzon L, Pacenti M, Masi G, Stefani AL, Fincati K, Palu G (2005) Loss of growth hormone secretagogue receptor 1a and overexpression of type 1b receptor transcripts in human adrenocortical tumors. Oncology 68: 414-421.
61. Chan CB, Cheng CH (2004) Identification and functional characterization of two alternatively spliced growth hormone secretagogue receptor transcripts from the pituitary of black seabream Acanthopagrus schlegeli. Mol Cell Endocrinol 214: 81-95.
62. Chu KM, Chow KB, Leung PK, Lau PN, Chan CB, Cheng CH, Wise H (2007) Over-expression of the truncated ghrelin receptor polypeptide attenuates the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors but has no effect on ghrelin-stimulated extracellular signal-regulated kinase 1/2 activity. Int J Biochem Cell Biol 39: 752-764.
63. Leung PK, Chow KB, Lau PN, Chu KM, Chan CB, Cheng CH, Wise H (2007) The truncated ghrelin receptor polypeptide (GHS-R1b) acts as a dominant-negative mutant of the ghrelin receptor. Cell Signal 19: 1011-1022.