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Breast Cancer Research
Published in: Breast Cancer Research 6/2008

Open Access 01-12-2008 | Research article

Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells

Authors: Bérengère Marty, Virginie Maire, Eléonore Gravier, Guillem Rigaill, Anne Vincent-Salomon, Marion Kappler, Ingrid Lebigot, Fathia Djelti, Audrey Tourdès, Pierre Gestraud, Philippe Hupé, Emmanuel Barillot, Francisco Cruzalegui, Gordon C Tucker, Marc-Henri Stern, Jean-Paul Thiery, John A Hickman, Thierry Dubois

Published in: Breast Cancer Research | Issue 6/2008

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Abstract

Introduction

Basal-like carcinomas (BLCs) and human epidermal growth factor receptor 2 overexpressing (HER2+) carcinomas are the subgroups of breast cancers that have the most aggressive clinical behaviour. In contrast to HER2+ carcinomas, no targeted therapy is currently available for the treatment of patients with BLCs. In order to discover potential therapeutic targets, we aimed to discover deregulated signalling pathways in human BLCs.

Methods

In this study, we focused on the oncogenic phosphatidylinositol 3-kinase (PI3K) pathway in 13 BLCs, and compared it with a control series of 11 hormonal receptor negative- and grade III-matched HER2+ carcinomas. The two tumour populations were first characterised by immunohistochemistry and gene expression. The PI3K pathway was then investigated by gene copy-number analysis, gene expression profiling and at a proteomic level using reverse-phase protein array technology and tissue microarray. The effects of the PI3K inhibition pathway on proliferation and apoptosis was further analysed in three human basal-like cell lines.

Results

The PI3K pathway was found to be activated in BLCs and up-regulated compared with HER2+ tumours as shown by a significantly increased activation of the downstream targets Akt and mTOR (mammalian target of rapamycin). BLCs expressed significantly lower levels of the tumour suppressor PTEN and PTEN levels were significantly negatively correlated with Akt activity within that population. PTEN protein expression correlated significantly with PTEN DNA copy number and more importantly, reduced PTEN DNA copy numbers were observed specifically in BLCs. Similar to human samples, basal-like cell lines exhibited an activation of PI3K/Akt pathway and low/lack PTEN expression. Both PI3K and mTOR inhibitors led to basal-like cell growth arrest. However, apoptosis was specifically observed after PI3K inhibition.

Conclusions

These data provide insight into the molecular pathogenesis of BLCs and implicate the PTEN-dependent activated Akt signalling pathway as a potential therapeutic target for the management of patients with poor prognosis BLCs.
Appendix
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Literature
1.
Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET: Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA. 2003, 100: 10393-10398. 10.1073/pnas.1732912100.CrossRefPubMedPubMedCentral
2.
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003, 100: 8418-8423. 10.1073/pnas.0932692100.CrossRefPubMedPubMedCentral
3.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn van de M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98: 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral
4.
Perou CM, Sorlie T, Eisen MB, Rijn van de M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed
5.
Huang E, Cheng SH, Dressman H, Pittman J, Tsou MH, Horng CF, Bild A, Iversen ES, Liao M, Chen CM, West M, Nevins JR, Huang AT: Gene expression predictors of breast cancer outcomes. Lancet. 2003, 361: 1590-1596. 10.1016/S0140-6736(03)13308-9.CrossRefPubMed
6.
van 't Veer LJ, Dai H, Vijver van de MJ, He YD, Hart AA, Mao M, Peterse HL, Kooy van der K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002, 415: 530-536. 10.1038/415530a.CrossRefPubMed
7.
Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005, 11: 5678-5685. 10.1158/1078-0432.CCR-04-2421.CrossRefPubMed
8.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, Rijn van de M, Perou CM: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004, 10: 5367-5374. 10.1158/1078-0432.CCR-04-0220.CrossRefPubMed
9.
Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, Lapuk A, Neve RM, Qian Z, Ryder T, Chen F, Feiler H, Tokuyasu T, Kingsley C, Dairkee S, Meng Z, Chew K, Pinkel D, Jain A, Ljung BM, Esserman L, Albertson DG, Waldman FM, Gray JW: Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell. 2006, 10: 529-541. 10.1016/j.ccr.2006.10.009.CrossRefPubMed
10.
Wirapati P, Sotiriou C, Kunkel S, Farmer P, Pradervand S, Haibe-Kains B, Desmedt C, Ignatiadis M, Sengstag T, Schutz F, Goldstein DR, Piccart M, Delorenzi M: Meta-analysis of gene-expression profiles in breast cancer: toward a unified understanding of breast cancer sub-typing and prognosis signatures. Breast Cancer Res. 2008, 10: R65-10.1186/bcr2124.CrossRefPubMedPubMedCentral
11.
Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J, Jatkoe T, Berns EM, Atkins D, Foekens JA: Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005, 365: 671-679.CrossRefPubMed
12.
Reis-Filho JS, Tutt AN: Triple negative tumours: a critical review. Histopathology. 2008, 52: 108-118. 10.1111/j.1365-2559.2008.03046.x.CrossRefPubMed
13.
Fadare O, Tavassoli FA: Clinical and pathologic aspects of basal-like breast cancers. Nat Clin Pract Oncol. 2008, 5: 149-159. 10.1038/ncponc1038.CrossRefPubMed
14.
Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, Foekens JA, Martens JW: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008, 68: 3108-3114. 10.1158/0008-5472.CAN-07-5644.CrossRefPubMed
15.
Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, Vijver van de MJ: Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res. 2007, 9: R65-10.1186/bcr1771.CrossRefPubMedPubMedCentral
16.
Couzin J: Cancer research. Probing the roots of race and cancer. Science. 2007, 315: 592-594. 10.1126/science.315.5812.592.CrossRefPubMed
17.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, et al: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005, 353: 1659-1672. 10.1056/NEJMoa052306.CrossRefPubMed
18.
Rakha EA, Reis-Filho JS, Ellis IO: Basal-like breast cancer: a critical review. J Clin Oncol. 2008, 26: 2568-2581. 10.1200/JCO.2007.13.1748.CrossRefPubMed
19.
Yehiely F, Moyano JV, Evans JR, Nielsen TO, Cryns VL: Deconstructing the molecular portrait of basal-like breast cancer. Trends Mol Med. 2006, 12: 537-544. 10.1016/j.molmed.2006.09.004.CrossRefPubMed
20.
Vincent-Salomon A, Gruel N, Lucchesi C, MacGrogan G, Dendale R, Sigal-Zafrani B, Longy M, Raynal V, Pierron G, de Mascarel I, Taris C, Stoppa-Lyonnet D, Pierga JY, Salmon R, Sastre-Garau X, Fourquet A, Delattre O, de Cremoux P, Aurias A: Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity. Breast Cancer Res. 2007, 9: R24-10.1186/bcr1666.CrossRefPubMedPubMedCentral
21.
Cleator S, Heller W, Coombes RC: Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007, 8: 235-244. 10.1016/S1470-2045(07)70074-8.CrossRefPubMed
22.
Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, Rodriguez-Gil Y, Martinez MA, Hernandez L, Hardisson D, Reis-Filho JS, Palacios J: Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol. 2007, 20: 474-481. 10.1038/modpathol.3800760.CrossRefPubMed
23.
Tokunaga E, Kimura Y, Mashino K, Oki E, Kataoka A, Ohno S, Morita M, Kakeji Y, Baba H, Maehara Y: Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast Cancer. 2006, 13: 137-144. 10.2325/jbcs.13.137.CrossRefPubMed
24.
Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmstrom PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R: PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 2005, 65: 2554-2559. 10.1158/0008-5472-CAN-04-3913.CrossRefPubMed
25.
Tokunaga E, Oki E, Kimura Y, Yamanaka T, Egashira A, Nishida K, Koga T, Morita M, Kakeji Y, Maehara Y: Coexistence of the loss of heterozygosity at the PTEN locus and HER2 overexpression enhances the Akt activity thus leading to a negative progesterone receptor expression in breast carcinoma. Breast Cancer Res Treat. 2007, 101: 249-257. 10.1007/s10549-006-9295-8.CrossRefPubMed
26.
Shaw RJ, Cantley LC: Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 2006, 441: 424-430. 10.1038/nature04869.CrossRefPubMed
27.
Engelman JA, Luo J, Cantley LC: The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006, 7: 606-619. 10.1038/nrg1879.CrossRefPubMed
28.
Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB: Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005, 4: 988-1004. 10.1038/nrd1902.CrossRefPubMed
29.
Liu W, Bagaitkar J, Watabe K: Roles of AKT signal in breast cancer. Front Biosci. 2007, 12: 4011-4019. 10.2741/2367.CrossRefPubMed
30.
Dillon RL, White DE, Muller WJ: The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer. Oncogene. 2007, 26: 1338-1345. 10.1038/sj.onc.1210202.CrossRefPubMed
31.
Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S, Uhlik M, Lin A, Du J, Qian YW, Zeckner DJ, Tucker-Kellogg G, Touchman J, Patel K, Mousses S, Bittner M, Schevitz R, Lai MH, Blanchard KL, Thomas JE: A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature. 2007, 448: 439-444. 10.1038/nature05933.CrossRefPubMed
32.
Kim MS, Jeong EG, Yoo NJ, Lee SH: Mutational analysis of oncogenic AKT E17K mutation in common solid cancers and acute leukaemias. Br J Cancer. 2008, 98: 1533-1535. 10.1038/sj.bjc.6604212.CrossRefPubMedPubMedCentral
33.
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, Vijver van de MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT: An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008, 68: 6084-6091. 10.1158/0008-5472.CAN-07-6854.CrossRefPubMedPubMedCentral
34.
Saal LH, Gruvberger-Saal SK, Persson C, Lovgren K, Jumppanen M, Staaf J, Jonsson G, Pires MM, Maurer M, Holm K, Koujak S, Subramaniyam S, Vallon-Christersson J, Olsson H, Su T, Memeo L, Ludwig T, Ethier SP, Krogh M, Szabolcs M, Murty VV, Isola J, Hibshoosh H, Parsons R, Borg A: Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet. 2008, 40: 102-107. 10.1038/ng.2007.39.CrossRefPubMed
35.
Azoulay S, Lae M, Freneaux P, Merle S, Al Ghuzlan A, Chnecker C, Rosty C, Klijanienko J, Sigal-Zafrani B, Salmon R, Fourquet A, Sastre-Garau X, Vincent-Salomon A: KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. Mod Pathol. 2005, 18: 1623-1631.PubMed
36.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, Vijver van de M, Wheeler TM, Hayes DF: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007, 25: 118-145. 10.1200/JCO.2006.09.2775.CrossRefPubMed
37.
Gulmann C, Sheehan KM, Kay EW, Liotta LA, Petricoin EF: Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancer. J Pathol. 2006, 208: 595-606. 10.1002/path.1958.CrossRefPubMed
38.
Chan SM, Ermann J, Su L, Fathman CG, Utz PJ: Protein microarrays for multiplex analysis of signal transduction pathways. Nat Med. 2004, 10: 1390-1396. 10.1038/nm1139.CrossRefPubMed
39.
Rigaill G, Hupe P, Almeida A, La Rosa P, Meyniel JP, Decraene C, Barillot E: ITALICS: an algorithm for normalization and DNA copy number calling for Affymetrix SNP arrays. Bioinformatics. 2008, 24: 768-774. 10.1093/bioinformatics/btn048.CrossRefPubMed
40.
Hupe P, Stransky N, Thiery JP, Radvanyi F, Barillot E: Analysis of array CGH data: from signal ratio to gain and loss of DNA regions. Bioinformatics. 2004, 20: 3413-3422. 10.1093/bioinformatics/bth418.CrossRefPubMed
41.
Wu Z, Irizarry RA, Gentleman R, Martinez-Murillo F, Spencer F: A Model-Based Background Adjustment for Oligonucleotide Expression Arrays. J Am Stat Assoc. 2004, 99: 909-917. 10.1198/016214504000000683.CrossRef
42.
43.
44.
Livasy CA, Perou CM, Karaca G, Cowan DW, Maia D, Jackson S, Tse CK, Nyante S, Millikan RC: Identification of a basal-like subtype of breast ductal carcinoma in situ. Hum Pathol. 2007, 38: 197-204. 10.1016/j.humpath.2006.08.017.CrossRefPubMed
45.
Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 2006, 19: 264-271. 10.1038/modpathol.3800528.CrossRefPubMed
46.
Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, et al: The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006, 7: 96-10.1186/1471-2164-7-96.CrossRefPubMedPubMedCentral
47.
Umemura S, Yoshida S, Ohta Y, Naito K, Osamura RY, Tokuda Y: Increased phosphorylation of Akt in triple-negative breast cancers. Cancer Sci. 2007, 98: 1889-1892. 10.1111/j.1349-7006.2007.00622.x.CrossRefPubMed
48.
Zhou X, Tan M, Stone Hawthorne V, Klos KS, Lan KH, Yang Y, Yang W, Smith TL, Shi D, Yu D: Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res. 2004, 10: 6779-6788. 10.1158/1078-0432.CCR-04-0112.CrossRefPubMed
49.
Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmstrom P, Memeo L, Isola J, Bendahl PO, Rosen N, Hibshoosh H, Ringner M, Borg A, Parsons R: Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA. 2007, 104: 7564-7569. 10.1073/pnas.0702507104.CrossRefPubMedPubMedCentral
50.
Depowski PL, Rosenthal SI, Ross JS: Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer. Mod Pathol. 2001, 14: 672-676. 10.1038/modpathol.3880371.CrossRefPubMed
51.
Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S: X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell. 2006, 9: 121-132. 10.1016/j.ccr.2006.01.013.CrossRefPubMed
52.
Adelaide J, Finetti P, Bekhouche I, Repellini L, Geneix J, Sircoulomb F, Charafe-Jauffret E, Cervera N, Desplans J, Parzy D, Schoenmakers E, Viens P, Jacquemier J, Birnbaum D, Bertucci F, Chaffanet M: Integrated profiling of basal and luminal breast cancers. Cancer Res. 2007, 67: 11565-11575. 10.1158/0008-5472.CAN-07-2536.CrossRefPubMed
53.
Barnache S, Le Scolan E, Kosmider O, Denis N, Moreau-Gachelin F: Phosphatidylinositol 4-phosphatase type II is an erythropoietin-responsive gene. Oncogene. 2006, 25: 1420-1423. 10.1038/sj.onc.1209187.CrossRefPubMed
54.
DeGraffenried LA, Fulcher L, Friedrichs WE, Grunwald V, Ray RB, Hidalgo M: Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway. Ann Oncol. 2004, 15: 1510-1516. 10.1093/annonc/mdh388.CrossRefPubMed
55.
Heinonen H, Nieminen A, Saarela M, Kallioniemi A, Klefstrom J, Hautaniemi S, Monni O: Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer. BMC Genomics. 2008, 9: 348-10.1186/1471-2164-9-348.CrossRefPubMedPubMedCentral
56.
Noh WC, Mondesire WH, Peng J, Jian W, Zhang H, Dong J, Mills GB, Hung MC, Meric-Bernstam F: Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res. 2004, 10: 1013-1023. 10.1158/1078-0432.CCR-03-0043.CrossRefPubMed
57.
Mondesire WH, Jian W, Zhang H, Ensor J, Hung MC, Mills GB, Meric-Bernstam F: Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells. Clin Cancer Res. 2004, 10: 7031-7042. 10.1158/1078-0432.CCR-04-0361.CrossRefPubMed
58.
Wan X, Harkavy B, Shen N, Grohar P, Helman LJ: Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene. 2007, 26: 1932-1940. 10.1038/sj.onc.1209990.CrossRefPubMed
59.
O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N: mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006, 66: 1500-1508. 10.1158/0008-5472.CAN-05-2925.CrossRefPubMedPubMedCentral
60.
Gharbi SI, Zvelebil MJ, Shuttleworth SJ, Hancox T, Saghir N, Timms JF, Waterfield MD: Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J. 2007, 404: 15-21. 10.1042/BJ20061489.CrossRefPubMedPubMedCentral
61.
Torbett NE, Luna-Moran A, Knight ZA, Houk A, Moasser M, Weiss W, Shokat KM, Stokoe D: A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isotype-selective inhibition. Biochem J. 2008, 415: 97-110. 10.1042/BJ20080639.CrossRefPubMedPubMedCentral
62.
Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, Zhang J, Signoretti S, Loda M, Roberts TM, Zhao JJ: Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature. 2008, 454: 776-779.PubMedPubMedCentral
63.
La Rosa P, Viara E, Hupe P, Pierron G, Liva S, Neuvial P, Brito I, Lair S, Servant N, Robine N, Manie E, Brennetot C, Janoueix-Lerosey I, Raynal V, Gruel N, Rouveirol C, Stransky N, Stern MH, Delattre O, Aurias A, Radvanyi F, Barillot E: VAMP: visualization and analysis of array-CGH, transcriptome and other molecular profiles. Bioinformatics. 2006, 22: 2066-2073. 10.1093/bioinformatics/btl359.CrossRefPubMed
Metadata
Title
Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells
Authors
Bérengère Marty
Virginie Maire
Eléonore Gravier
Guillem Rigaill
Anne Vincent-Salomon
Marion Kappler
Ingrid Lebigot
Fathia Djelti
Audrey Tourdès
Pierre Gestraud
Philippe Hupé
Emmanuel Barillot
Francisco Cruzalegui
Gordon C Tucker
Marc-Henri Stern
Jean-Paul Thiery
John A Hickman
Thierry Dubois
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2204

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