nach oben

Erschienen in:

01.09.2016 | Original Article

Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines

verfasst von: Erica Gentilin, Mariella Minoia, Marta Bondanelli, Federico Tagliati, Ettore C. degli Uberti, Maria Chiara Zatelli

Erschienen in: Endocrine | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Abstract

Growth Hormone may influence neoplastic development of endometrial epithelium towards endometrial adenocarcinoma, which is one of the most occurring tumors in acromegalic patients. Since chemoresistance often develops in advanced endometrial adenocarcinoma, we investigated whether Growth Hormone might influence the development of chemoresistance to drugs routinely employed in endometrial adenocarcinoma treatment, such as Doxorubicin, Cisplatin, and Paclitaxel. Growth Hormone and Growth Hormone receptor expression was assessed by immunofluorescence in two endometrial adenocarcinoma cell lines, AN3 CA and HEC-1-A cells. Growth Hormone effects were assessed investigating cell viability, caspase3/7 activation, ERK1/2, and protein kinase C delta protein expression. AN3 CA and HEC-1-A cells display Growth Hormone and Growth Hormone receptor. Growth Hormone does not influence cell viability in both cells lines, but significantly reduces caspase 3/7 activation in AN3 CA cells, an effect blocked by a Growth Hormone receptor antagonist. Growth Hormone rescues AN3 CA cells from the inhibitory effects of Doxorubicin and Cisplatin on cell viability, while it has no effect on Paclitaxel. Growth Hormone does not influence the pro-apoptotic effects of Doxorubicin, but is capable of rescuing AN3 CA cells from the pro-apoptotic effects of Cisplatin. On the other hand, Growth Hormone did not influence the effects of Doxorubicin and Paclitaxel on HEC-1A cell viability. The protective action of Growth Hormone towards the effects of Doxorubicin may be mediated by ERK1/2 activation, while the pro-apoptotic effects of Cisplatin may be mediated by protein kinase C delta inhibition. All together our results indicate that Growth Hormone may differentially contribute to endometrial adenocarcinoma chemoresistance. This may provide new insights on novel therapies against endometrial adenocarcinoma chemoresistant aggressive tumors.

Nur mit Berechtigung zugänglich

1..

A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, M.J. Thun, Cancer statistics 2009. CA Cancer J. Clin. 59, 225–249 (2009)CrossRefPubMed

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D.M. Parkin, D. Forman, F. Bray, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359–E386 (2015)CrossRefPubMed

P. Morice, A. Leary, C. Creutzberg, N. Abu-Rustum, E. Darai, Endometrial cancer. Lancet 387, 1094–1108 (2016)CrossRefPubMed

P. Chaudhry, E. Asselin, Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr. Relat. Cancer 16, 363–380 (2009)CrossRefPubMed

M. Bidosee, R. Karry, E. Weiss-Messer, R.J. Barkey, Growth hormone affects gene expression and proliferation in human prostate cancer cells. Int. J. Androl. 34, 124–137 (2011)CrossRefPubMed

V. Pandey, J.K. Perry, K.M. Mohankumar, X.J. Kong, S.M. Liu, Z.S. Wu, M.D. Mitchell, T. Zhu, P.E. Lobie, Autocrine human growth hormone stimulates oncogenicity of endometrial carcinoma cells. Endocrinology 149, 3909–3919 (2008)CrossRefPubMedPubMedCentral

M. Slater, M. Cooper, C.R. Murphy, Human growth hormone and interleukin-6 are upregulated in endometriosis and endometrioid adenocarcinoma. Acta Histochem. 108, 13–18 (2006)CrossRefPubMed

D. Ayalon, M.R. Peyser, R. Limor, J.B. Lessing, R. Ravid, Paradoxical hypersecretion of growth hormone in patients with endometrial atypical hyperplasia and carcinoma. Effect of hysterectomy. Gynecol. Obstet. Invest. 13, 9–16 (1982)CrossRefPubMed

M.C. Zatelli, M. Minoia, D. Molè, V. Cason, F. Tagliati, A. Margutti, M. Bondanelli, M.R. Ambrosio, E. degli Uberti, Growth hormone excess promotes breast cancer chemoresistance. J. Clin. Endocrinol. Metab. 94, 3931–3938 (2009)CrossRefPubMed

10.

M. Minoia, E. Gentilin, D. Molè, M. Rossi, C. Filieri, F. Tagliati, A. Baroni, M.R. Ambrosio, E. degli Uberti, M.C. Zatelli, Growth hormone receptor blockade inhibits growth hormone-induced chemoresistance by restoring cytotoxic-induced apoptosis in breast cancer cells independently of estrogen receptor expression. J. Clin. Endocrinol. Metab. 97, E907–E916 (2012)CrossRefPubMed

11.

A. Bałdys-Waligórska, A. Krzentowskam, F. Gołkowski, G. Sokołowski, A. Hubalewska-Dydejczyk, The prevalence of benign and malignant neoplasms in acromegalic patients.. Endokrynol. Pol. 61, 29–34 (2010)PubMed

12.

D. Molè, T. Gagliano, E. Gentilin, F. Tagliati, C. Pasquali, M.R. Ambrosio, G. Pansini, E.C. degli Uberti, M.C. Zatelli, Targeting protein kinase C by Enzastaurin restrains proliferation and secretion in human pancreatic endocrine tumors. Endocr. Relat. Cancer. 18, 439–450 (2011)CrossRefPubMed

13.

E. Gentilin, D. Molè, T. Gagliano, M. Minoia, M.R. Ambrosio, E.C. degli Uberti, M.C. Zatelli, Inhibitory effects of mitotane on viability and secretory activity in mouse gonadotroph cell lines. Reprod. Toxicol. 45, 71–76 (2014)CrossRefPubMed

14.

F. Tagliati, E. Gentilin, M. Buratto, D. Molé, E.C. degli Uberti, M.C. Zatelli, Magmas, a gene newly identified as overexpressed in human and mouse ACTH-secreting pituitary adenomas, protects pituitary cells from apoptotic stimuli. Endocrinology 151, 4635–4642 (2010)CrossRefPubMed

15.

T. Gagliano, E. Gentilin, K. Benfini, C. Di Pasquale, M. Tassinari, S. Falletta, C. Feo, F. Tagliati, E.D. degli Uberti, M.C. Zatelli, Mitotane enhances doxorubicin cytotoxic activity by inhibiting P-gp in human adrenocortical carcinoma cells. Endocrine 47, 943–951 (2014)CrossRefPubMed

16.

E. Gentilin, F. Tagliati, C. Filieri, D. Molè, M. Minoia, M.R. Ambrosio, E.C. degli Uberti, M.C. Zatelli, miR-26a plays an important role in cell cycle regulation in ACTH-secreting pituitary adenomas by modulating protein kinase Cδ. Endocrinology 154, 1690–1700 (2013)CrossRefPubMedPubMedCentral

17.

B. Kharma, T. Baba, M. Mandai, N. Matsumura, S.K. Murphy, H.S. Kang, K. Yamanoi, J. Hamanishi, K. Yamaguchi, Y. Yoshioka, I. Konishi, Utilization of genomic signatures to identify high-efficacy candidate drugs for chemorefractory endometrial cancers. Int. J. Cancer 133, 2234–2244 (2013)CrossRefPubMed

18.

K. Chitcholtan, P.H. Sykes, J.J. Evans, The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer. J. Transl. Med. 10, 38 (2012)CrossRefPubMedPubMedCentral

19.

S. Mohanty, J. Huang, A. Basu, Enhancement of cisplatin sensitivity of cisplatin-resistant human cervical carcinoma cells by bryostatin 1. Clin. Cancer Res. 11, 6730–6737 (2005)CrossRefPubMed

20.

A. Tejerizo-García, J.S. Jiménez-López, J.L. Muñoz-González, S. Bartolomé-Sotillos, L. Marqueta-Marqués, G. López-González, J.F. Gómez, Overall survival and disease-free survival in ndometrial cancer: prognostic factors in 276 patients. Onco. Targets Ther. 9, 1305–1313 (2013)PubMed

21.

P. Chaudhry, E. Asselin, Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr. Relat. Cancer 16, 363–380 (2009)CrossRefPubMed

22.

M. Sbracia, F. Scarpellini, R. Poverini, P.L. Alo, G. Rossi, U. Di Tondo, Immunohistochemical localization of the growth hormone in human endometrium and decidua. Am. J. Reprod. Immunol. 51, 112–116 (2004)CrossRefPubMed

23.

K.L. Hull, S. Harvey, Growth hormone and reproduction: a review of endocrine and autocrine/paracrine interactions. Int. J. Endocrinol. 2014, 234014 (2014)CrossRefPubMedPubMedCentral

24.

J.K. Perry, K.M. Mohankumar, B.S. Emerald, H.C. Mertani, P.E. Lobie, The contribution of growth hormone to mammary neoplasia. J. Mammary Gland Biol. Neoplasia 13, 131–145 (2008)CrossRefPubMedPubMedCentral

25.

Z. Yurkovetsky, S. Ta’asan, S. Skates, A. Rand, A. Lomakin, F. Linkov, A. Marrangoni, L. Velikokhatnaya, M. Winans, E. Gorelik, G.L. Maxwell, K. Lu, A. Lokshin, Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin. Gynecol. Oncol. 107, 58–65 (2008)CrossRef

26.

27.

J.R. González-Juanatey, R. Piñeiro, M.J. Iglesias, O. Gualillo, P.A. Kelly, C. Diéguez, F. Lago, GH prevents apoptosis in cardiomyocytes cultured in vitro through a calcineurin-dependent mechanism. J. Endocrinol. 180, 325–335 (2004)CrossRefPubMed

28.

F. Bogazzi, F. Ultimieri, F. Raggi, D. Russo, R. Vanacore, C. Guida, S. Brogioni, C. Cosci, M. Gasperi, L. Bartalena, E. Martino, Growth hormone inhibits apoptosis in human colonic cancer cell lines: antagonistic effects of peroxisome proliferator activated receptor-gamma ligands. Endocrinology 145, 3353–3362 (2004)CrossRefPubMed

29.

G.F. Fleming, Systematic chemotherapy for uterine carcinoma: metastatic and adjuvant. J. Clin. Oncol. 25, 2983–2990 (2007)CrossRefPubMed

30.

K.M. Moxley, D.S. McMeekin, Endometrial carcinoma: a review of chemotherapy, drug resistance, and the search for new agents. Oncologist 15, 1026–1033 (2010)CrossRefPubMedPubMedCentral

31.

S.A. Byron, D.C. Loch, P.M. Pollock, Fibroblast growth factor receptor inhibition synergizes with Paclitaxel and Doxorubicin in endometrial cancer cells. Int. J. Gynecol. Cancer 22, 1517–1526 (2012)PubMed

32.

J.W. Wallen, R.L. Cate, D.M. Kiefer, M.W. Riemen, D. Martinez, R.M. Hoffman, P.K. Donahoe, D.D. Von Hoff, B. Pepinsky, A. Oliff, Minimal antiproliferative effect of recombinant müllerian inhibiting substance on gynecological tumor cell lines and tumor explants. Cancer Res. 49, 2005–2011 (1989)PubMed

33.

34.

H.S. Chon, D.C. Marchion, Y. Xiong, N. Chen, E. Bicaku, X.B. Stickles, N. Bou Zgheib, P.L. Judson, A. Hakam, J. Gonzalez-Bosquet, R.M. Wenham, S.M. Apte, J.M. Lancaster, The BCL2 antagonist of cell death pathway influences endometrial cancer cell sensitivity to cisplatin. Gynecol. Oncol. 124, 119–124 (2012)CrossRefPubMed

35.

V. Gagnon, I. Mathieu, E. Sexton, K. Leblanc, E. Asselin, AKT involvement in cisplatin chemoresistance of human uterine cancer cells. Gynecol. Oncol. 94, 785–795 (2004)CrossRefPubMed

36.

A. Rouette, S. Parent, J. Girouard, V. Leblanc, E. Asselin, Cisplatin increases B-cell-lymphoma-2 expression via activation of protein kinase C and Akt2 in endometrial cancer cells. Int. J. Cancer 130, 1755–1767 (2012)CrossRefPubMed

37.

J.W. Roh, J. Huang, W. Hu, X. Yang, N.B. Jennings, V. Sehgal, B.H. Sohn, H.D. Han, S.J. Lee, D. Thanapprapasr, J. Bottsford-Miller, B. Zand, H.J. Dalton, R.A. Previs, A.N. Davis, K. Matsuo, J.S. Lee, P. Ram, R.L. Coleman, A.K. Sood, Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer. Clin. Cancer Res. 20, 2740–2750 (2014)CrossRefPubMedPubMedCentral

38.

C.S. Lin, P.C. Chen, C.K. Wang, C.W. Wang, Y.J. Chang, C.J. Tai, C.J. Tai, Antitumor effects and biological mechanism of action of the aqueous extract of the camptotheca acuminata fruit in human endometrial carcinoma cells. Evid. Based Complement. Alternat. Med. 2014, 564810 (2014)PubMedPubMedCentral

39.

T. Beckers, T. Reissmann, M. Schmidt, A.M. Burger, H.H. Fiebig, U. Vanhoefer, H. Pongratz, H. Hufsky, J. Hockemeyer, M. Frieser, S. Mahboobi, 2-aroylindoles, a novel class of potent, orally active small molecule tubulin inhibitors. Cancer Res. 62, 3113–3119 (2002)PubMed

40.

G.F. Weber (ed.), DNA Damaging Drugs, in Molecular therapies of cancer, (Springer International Publishing, 2015), p. 59

41.

P.D. Sadowitz, B.A. Hubbard, J.C. Dabrowiak, J. Goodisman, K.A. Tacka, M.K. Aktas, M.J. Cunningham, R.L. Dubowy, A.K. Souid, Kinetics of cisplatin binding to cellular DNA and modulations by thiol-blocking agents and thiol drugs. Drug Metab. Dispos. 30, 183–190 (2002)CrossRefPubMed

42.

J. Spratlin, M.B. Sawyer, Pharmacogenetics of paclitaxel metabolism. Crit. Rev. Oncol. Hematol. 61, 222–229 (2007)CrossRefPubMed

43.

A. Henningsson, A. Sparreboom, M. Sandström, A. Freijs, R. Larsson, J. Bergh, P. Nygren, M.O. Karlsson, Population pharmacokinetic modelling of unbound and total plasma concentrations of paclitaxel in cancer patients. Eur. J. Cancer 39, 1105–1114 (2003)CrossRefPubMed

44.

S. Dasari, P.B. Tchounwou, Cisplatin in cancer therapy: molecular mechanisms of action. Eur. J. Pharmacol. 740, 364–378 (2014)CrossRefPubMed

45.

H. Cortés-Funes, C. Coronado, Role of anthracyclines in the era of targeted therapy. Cardiovasc. Toxicol. 7, 56–60 (2007)CrossRefPubMed

46.

C.F. Thorn, C. Oshiro, S. Marsh, T. Hernandez-Boussard, H. McLeod, T.E. Klein, R.B. Altman, Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet. Genomics 21, 440–446 (2011)CrossRefPubMedPubMedCentral

47.

Z.H. Siddik, Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265–7279 (2003)CrossRefPubMed

48.

B.A. Weaver, How Taxol/paclitaxel kills cancer cells. Mol. Biol. Cell 25, 2677–2681 (2014)CrossRefPubMedPubMedCentral

49.

I.E. Elijah, L.K. Branski, C.C. Finnerty, D.N. Herndon, The GH/IGF-1 system in critical illness. Best Pract. Res. Clin. Endocrinol. Metab. 25, 759–767 (2011)CrossRefPubMedPubMedCentral

50.

S. Shu, Y. Yang, X. Li, T. Li, Y. Zhang, C. Xu, C. Liang, X. Wang, Down-regulation of IGF-1R expression inhibits growth and enhances chemosensitivity of endometrial carcinoma in vitro. Mol. Cell Biochem. 353, 225–339 (2011)CrossRefPubMed

51.

C. Hodge, J. Liao, M. Stofega, K. Guan, C. Carter-Su, J. Schwartz, Growth hormone stimulates phosphorylation and activation of elk-1 and expression of c-fos, egr-1, and junB through activation of extracellular signal-regulated kinases 1 and 2. J. Biol. Chem. 273, 31327–31336 (1998)CrossRefPubMed

52.

K.K. Kim, A. Han, N. Yano, J.R. Ribeiro, E. Lokich, R.K. Singh, R.G. Moore, Tetrathiomolybdate mediates cisplatin-induced p38 signaling and EGFR degradation and enhances response to cisplatin therapy in gynecologic cancers. Sci. Rep. 5, 15911 (2015)CrossRefPubMedPubMedCentral

53.

R. Roskoski, ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol. Res. 66, 105–143 (2012)CrossRefPubMed

54.

S.Q. Liu, J.P. Yu, H.G. Yu, P. Lv, H.L. Chen, Activation of Akt and ERK signalling pathways induced by etoposide confer chemoresistance in gastric cancer cells. Dig. Liver Dis. 38, 310–318 (2006)CrossRefPubMed

55.

C. Denglin, X. Derong, G. Shuangshuang, Y. Qiong, J. Zhimin, B. Zhuofei, M. Wen, ERK signaling pathway may induce gemcitabine chemoresistance in pancreatic cancer cell line SW1990 by regulating the expression of mdr-1 and RRM1 gene. Chin. Ger. J. Clin. Oncol. 8, 37–41 (2009)CrossRef

56.

S. Liu, J. Wang, W. Niu, E. Liu, J. Wang, C. Peng, P. Lin, B. Wang, A.Q. Khan, H. Gao, B. Liang, M. Shahbaz, J. Niu, The β6-integrin-ERK/MAP kinase pathway contributes to chemo resistance in colon cancer. Cancer Lett. 328, 325–334 (2013)CrossRefPubMed

57.

U. Kikkawa, H. Matsuzaki, T. Yamamoto, Protein kinase C delta (PKC delta): activation mechanisms and functions. J. Biochem. 132, 831–839 (2002)CrossRefPubMed

58.

E. Gentilin, C. Di Pasquale, T. Gagliano, F. Tagliati, K. Benfini, M.R. Ambrosio, M. Bondanelli, E.C. degli Uberti, M.C. Zatelli, Protein Kinase C Delta restrains growth in ACTH-secreting pituitary adenoma cells. Mol. Cell Endocrinol. 419, 252–258 (2016)CrossRefPubMed

59.

J. Huang, S. Mohanty, A. Basu, Cisplatin resistance is associated with deregulation in protein kinase C-delta. Biochem. Biophys. Res. Commun. 316, 1002–1008 (2004)CrossRefPubMed

60.

A. Basu, M.D. Woolard, C.L. Johnson, Involvement of protein kinase C-delta in DNA damage-induced apoptosis. Cell Death Differ. 8, 899–908 (2001)CrossRefPubMed

Titel: Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines
verfasst von: Erica Gentilin
Mariella Minoia
Marta Bondanelli
Federico Tagliati
Ettore C. degli Uberti
Maria Chiara Zatelli
Publikationsdatum: 01.09.2016
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 3/2017
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-016-1085-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2017

Risk factors of type 1 gastric neuroendocrine neoplasia in patients with chronic atrophic gastritis. A retrospective, multicentre study

STEAP4 expression in human islets is associated with differences in body mass index, sex, HbA1c, and inflammation

Erratum to: Thyroid hormones alterations during acute liver failure: possible underlying mechanisms and consequences

Epidemiology, management and outcomes of Graves’ disease—real life data

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

Leptin directly stimulates parathyroid hormone secretion

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin