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01.12.2009 | Preclinical Study

Opposite effects of protein kinase C beta1 (PKCβ1) and PKCε in the metastatic potential of a breast cancer murine model

verfasst von: Valeria C. Grossoni, Laura B. Todaro, Marcelo G. Kazanietz, Elisa D. Bal de Kier Joffé, Alejandro J. Urtreger

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2009

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Abstract

In this paper we investigated whether protein kinase C (PKC) β1 and PKCε, members of the classical and novel PKC family, respectively, induce phenotypic alterations that could be associated with tumor progression and metastatic dissemination in a murine model of breast cancer. Stable overexpression of PKCβ1 in LM3 cells altered their ability to proliferate, adhere, and survive, and impaired their tumorigenicity and metastatic capacity. Moreover, PKCβ1 induced the re-expression of fibronectin, an extracellular matrix glycoprotein which loss has been associated with the acquisition of a transformed phenotype in different cell models, and exerted an important inhibition on proteases production, effects that probably impact on LM3 invasiveness and dissemination. Conversely, PKCε overexpression enhanced LM3 survival, anchorage-independent growth, and caused a significant increase in spontaneous lung metastasis. Our results suggest PKCβ1 functions as an inhibitory protein for tumor growth and metastasis dissemination whereas PKCε drives metastatic dissemination without affecting primary tumor growth.

Dekker LV, Parker PJ (1994) Protein kinase C—a question of specificity. Trends Biochem Sci 19:73–77. doi:10.1016/0968-0004(94)90038-8 CrossRefPubMed

Kiley SC, Clark KJ, Duddy SK et al (1999) Increased protein kinase C delta in mammary tumor cells: relationship to transformation and metastatic progression. Oncogene 18:6748–6757. doi:10.1038/sj.onc.1203101 CrossRefPubMed

Nishizuka Y (1995) Protein kinase C and lipid signaling for sustained cellular responses. FASEB J 9:484–496PubMed

Mellor H, Parker PJ (1998) The extended protein kinase C superfamily. Biochem J 332(Pt 2):281–292PubMed

Newton AC (1997) Regulation of protein kinase C. Curr Opin Cell Biol 9:161–167. doi:10.1016/S0955-0674(97)80058-0 CrossRefPubMed

Newton AC (1995) Protein kinase C: structure, function, and regulation. J Biol Chem 270:28495–28498. doi:10.1074/jbc.270.43.25526 CrossRefPubMed

Gordge PC, Hulme MJ, Clegg RA et al (1996) Elevation of protein kinase A and protein kinase C activities in malignant as compared with normal human breast tissue. Eur J Cancer 32A:2120–2126. doi:10.1016/S0959-8049(96)00255-9 CrossRefPubMed

McCracken MA, Miraglia LJ, McKay RA et al (2003) Protein kinase C delta is a prosurvival factor in human breast tumor cell lines. Mol Cancer Ther 2:273–281PubMed

Gokmen-Polar Y, Murray NR, Velasco MA et al (2001) Elevated protein kinase C beta II is an early promotive event in colon carcinogenesis. Cancer Res 61:1375–1381PubMed

10.

Regala RP, Weems C, Jamieson L et al (2005) Atypical protein kinase C iota is an oncogene in human non-small cell lung cancer. Cancer Res 65:8905–8911. doi:10.1158/0008-5472.CAN-05-2372 CrossRefPubMed

11.

Lee SA, Karaszkiewicz JW, Anderson WB (1992) Elevated level of nuclear protein kinase C in multidrug-resistant MCF-7 human breast carcinoma cells. Cancer Res 52:3750–3759PubMed

12.

Ways DK, Kukoly CA, deVente J et al (1995) MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype. J Clin Invest 95:1906–1915. doi:10.1172/JCI117872 CrossRefPubMed

13.

Tonetti DA, Chisamore MJ, Grdina W et al (2000) Stable transfection of protein kinase C alpha cDNA in hormone-dependent breast cancer cell lines. Br J Cancer 83:782–791. doi:10.1054/bjoc.2000.1326 CrossRefPubMed

14.

Koren R, Ben Meir D, Langzam L et al (2004) Expression of protein kinase C isoenzymes in benign hyperplasia and carcinoma of prostate. Oncol Rep 11:321–326PubMed

15.

Pan Q, Bao LW, Kleer CG et al (2005) Protein kinase C epsilon is a predictive biomarker of aggressive breast cancer and a validated target for RNA interference anticancer therapy. Cancer Res 65:8366–8371. doi:10.1158/0008-5472.CAN-05-0553 CrossRefPubMed

16.

Jiang XH, Lam SK, Lin MC et al (2002) Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-beta(1)-dependent pathway. Oncogene 21:6113–6122. doi:10.1038/sj.onc.1205778 CrossRefPubMed

17.

Teicher BA, Menon K, Alvarez E et al (2001) Antiangiogenic and antitumor effects of a protein kinase C beta inhibitor in human hepatocellular and gastric cancer xenografts. In Vivo 15:185–193PubMed

18.

Goldstein DR, Cacace AM, Weinstein IB (1995) Overexpression of protein kinase C beta 1 in the SW480 colon cancer cell line causes growth suppression. Carcinogenesis 16:1121–1126. doi:10.1093/carcin/16.5.1121 CrossRefPubMed

19.

Macfarlane DE, Manzel L (1994) Activation of beta-isozyme of protein kinase C (PKC beta) is necessary and sufficient for phorbol ester-induced differentiation of HL-60 promyelocytes. Studies with PKC beta-defective PET mutant. J Biol Chem 269:4327–4331PubMed

20.

Powell MB, Rosenberg RK, Graham MJ et al (1993) Protein kinase C beta expression in melanoma cells and melanocytes: differential expression correlates with biological responses to 12-O-tetradecanoylphorbol 13-acetate. J Cancer Res Clin Oncol 119:199–206. doi:10.1007/BF01624431 CrossRefPubMed

21.

Wu D, Foreman TL, Gregory CW et al (2002) Protein kinase cepsilon has the potential to advance the recurrence of human prostate cancer. Cancer Res 62:2423–2429PubMed

22.

McJilton MA, Van Sikes C, Wescott GG et al (2003) Protein kinase Cepsilon interacts with Bax and promotes survival of human prostate cancer cells. Oncogene 22:7958–7968. doi:10.1038/sj.onc.1206795 CrossRefPubMed

23.

Aziz MH, Manoharan HT, Verma AK (2007) Protein kinase C epsilon, which sensitizes skin to sun’s UV radiation-induced cutaneous damage and development of squamous cell carcinomas, associates with Stat3. Cancer Res 67:1385–1394. doi:10.1158/0008-5472.CAN-06-3350 CrossRefPubMed

24.

Lin W, Wang SM, Huang TF et al (2002) Differential regulation of fibronectin fibrillogenesis by protein kinases A and C. Connect Tissue Res 43:22–31. doi:10.1080/713713428 CrossRefPubMed

25.

Urtreger A, Porro F, Puricelli L et al (1998) Expression of RGD minus fibronectin that does not form extracellular matrix fibrils is sufficient to decrease tumor metastasis. Int J Cancer 78:233–241. doi:10.1002/(SICI)1097-0215(19981005)78:2<233::AID-IJC18>3.0.CO;2-BCrossRefPubMed

26.

Green KA, Lund LR (2005) ECM degrading proteases and tissue remodelling in the mammary gland. Bioessays 27:894–903. doi:10.1002/bies.20281 CrossRefPubMed

27.

Ossowski L, Biegel D, Reich E (1979) Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Cell 16:929–940. doi:10.1016/0092-8674(79)90108-9 CrossRefPubMed

28.

Thomasset N, Lochter A, Sympson CJ et al (1998) Expression of autoactivated stromelysin-1 in mammary glands of transgenic mice leads to a reactive stroma during early development. Am J Pathol 153:457–467PubMed

29.

Skrzydlewska E, Sulkowska M, Koda M et al (2005) Proteolytic–antiproteolytic balance and its regulation in carcinogenesis. World J Gastroenterol 11:1251–1266PubMed

30.

Juarez J, Clayman G, Nakajima M et al (1993) Role and regulation of expression of 92-kDa type-IV collagenase (MMP-9) in 2 invasive squamous-cell-carcinoma cell lines of the oral cavity. Int J Cancer 55:10–18. doi:10.1002/ijc.2910550104 CrossRefPubMed

31.

Aguirre-Ghiso JA, Alonso DF, Farias EF et al (1997) Overproduction of urokinase-type plasminogen activator is regulated by phospholipase D and protein kinase C-dependent pathways in murine mammary adenocarcinoma cells. BBA 1356:171–184PubMed

32.

Aguirre Ghiso JA, Alonso DF, Farias EF et al (1999) Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. Eur J Biochem 263:295–304. doi:10.1046/j.1432-1327.1999.00507.x CrossRefPubMed

33.

Masso-Welch PA, Verstovsek G, Ip MM (1999) Alterations in the expression and localization of protein kinase C isoforms during mammary gland differentiation. Eur J Cell Biol 78:497–510PubMed

34.

Egeblad M, Werb Z (2002) New functions for matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174. doi:10.1038/nrc745 CrossRefPubMed

35.

Urtreger AJ, Ladeda V, Vidal MC et al (1997) Modulation of fibronectin expression and proteolytic activity associated with the invasive and metastatic phenotype in two new murine mammary tumor cell lines. Int J Oncol 11:489–496

36.

Urtreger AJ, Grossoni VC, Falbo KB et al (2005) Atypical protein kinase C-zeta modulates clonogenicity, motility, and secretion of proteolytic enzymes in murine mammary cells. Mol Carcinog 42:29–39. doi:10.1002/mc.20066 CrossRefPubMed

37.

Urtreger AJ, Aguirre Ghiso JA, Werbajh SE et al (1999) Involvement of fibronectin in the regulation of urokinase production and binding in murine mammary tumor cells. Int J Cancer 82:748–753. doi:10.1002/(SICI)1097-0215(19990827)82:5<748::AID-IJC20>3.0.CO;2-RCrossRefPubMed

38.

Alonso DF, Farias EF, Urtreger A et al (1996) Characterization of F3II, a sarcomatoid mammary carcinoma cell line originated from a clonal subpopulation of a mouse adenocarcinoma. J Surg Oncol 62:288–297. doi:10.1002/(SICI)1096-9098(199608)62:4<288::AID-JSO14>3.0.CO;2-1CrossRefPubMed

39.

Aguirre Ghiso JA, Kovalski K, Ossowski L (1999) Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J Cell Biol 147:89–104. doi:10.1083/jcb.147.1.89 CrossRefPubMed

40.

Zhong M, Lu Z, Foster DA (2002) Downregulating PKC delta provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression. Oncogene 21:1071–1078. doi:10.1038/sj.onc.1205165 CrossRefPubMed

41.

Gliki G, Wheeler-Jones C, Zachary I (2002) Vascular endothelial growth factor induces protein kinase C (PKC)-dependent Akt/PKB activation and phosphatidylinositol 3′-kinase-mediates PKC delta phosphorylation: role of PKC in angiogenesis. Cell Biol Int 26:751–759. doi:10.1016/S1065-6995(02)90926-1 CrossRefPubMed

42.

Tanaka Y, Gavrielides MV, Mitsuuchi Y et al (2003) Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway. J Biol Chem 278:33753–33762. doi:10.1074/jbc.M303313200 CrossRefPubMed

43.

Li L, Sampat K, Hu N et al (2006) Protein kinase C negatively regulates Akt activity and modifies UVC-induced apoptosis in mouse keratinocytes. J Biol Chem 281:3237–3243. doi:10.1074/jbc.M512167200 CrossRefPubMed

44.

Bumaschny V, Urtreger A, Diament M et al (2004) Malignant myoepithelial cells are associated with the differentiated papillary structure and metastatic ability of a syngeneic murine mammary adenocarcinoma model. Breast Cancer Res 6:R116–R129. doi:10.1186/bcr757 CrossRefPubMed

45.

Mao Y, Schwarzbauer JE (2005) Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 24:389–399. doi:10.1016/j.matbio.2005.06.008 CrossRefPubMed

46.

Ruoslahti E (1984) Fibronectin in cell adhesion and invasion. Cancer Metastas Rev 3:43–51. doi:10.1007/BF00047692 CrossRef

47.

Siskova Z, Baron W, de Vries H et al (2006) Fibronectin impedes “myelin” sheet-directed flow in oligodendrocytes: a role for a beta 1 integrin-mediated PKC signaling pathway in vesicular trafficking. Mol Cell Neurosci 33:150–159. doi:10.1016/j.mcn.2006.07.001 CrossRefPubMed

48.

Ha H, Yu MR, Lee HB (2001) High glucose-induced PKC activation mediates TGF-beta 1 and fibronectin synthesis by peritoneal mesothelial cells. Kidney Int 59:463–470. doi:10.1046/j.1523-1755.2001.059002463.x CrossRefPubMed

49.

Werbajh SE, Urtreger AJ, Puricelli LI et al (1998) Downregulation of fibronectin transcription in highly metastatic adenocarcinoma cells. FEBS Lett 440:277–281. doi:10.1016/S0014-5793(98)01473-2 CrossRefPubMed

50.

Montaner S, Ramos A, Perona R et al (1995) Overexpression of PKC zeta in NIH3T3 cells does not induce cell transformation nor tumorigenicity and does not alter NF kappa B activity. Oncogene 10:2213–2220PubMed

51.

Andreasen PA, Kjoller L, Christensen L et al (1997) The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 72:1–22. doi:10.1002/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO;2-ZCrossRefPubMed

52.

Ranuncolo SM, Armanasco E, Cresta C et al (2003) Plasma MMP-9 (92 kDa-MMP) activity is useful in the follow-up and in the assessment of prognosis in breast cancer patients. Int J Cancer 20:745–751. doi:10.1002/ijc.11288 CrossRef

53.

Mazzoni E, Adam A, Bal de Kier Joffe ED et al (2003) Immortalized mammary epithelial cells overexpressing protein kinase C gamma acquire a malignant phenotype and become tumorigenic in vivo. Mol Cancer Res 1:776–787PubMed

54.

Sliva D (2004) Signaling pathways responsible for cancer cell invasion as targets for cancer therapy. Curr Cancer Drug Targets 4:327–336. doi:10.2174/1568009043332961 CrossRefPubMed

55.

Ron D, Kazanietz MG (1999) New insights into the regulation of protein kinase C and novel phorbol ester receptors. FASEB J 13:1658–1676PubMed

56.

Griner EM, Kazanietz MG (2007) Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer 7:281–294. doi:10.1038/nrc2110 CrossRefPubMed

Titel: Opposite effects of protein kinase C beta1 (PKCβ1) and PKCε in the metastatic potential of a breast cancer murine model
verfasst von: Valeria C. Grossoni
Laura B. Todaro
Marcelo G. Kazanietz
Elisa D. Bal de Kier Joffé
Alejandro J. Urtreger
Publikationsdatum: 01.12.2009
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2009
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0299-4

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Opposite effects of protein kinase C beta1 (PKCβ1) and PKCε in the metastatic potential of a breast cancer murine model

Abstract

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