Roles of AKT signal in breast cancer

Frontiers in Bioscience

Volumn 12, Issue 11, 2007, Pages 4011-4019

  Liu, Wen ^a   Bagaitkar, Juhi ^a   Watabe, Kounosuke ^a  

^a SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Akt; Breast; Cancer; Neoplasia; Review; Tumor

Indexed keywords

PROTEIN KINASE B; PROTEIN KINASE INHIBITOR;

BREAST TUMOR; DISEASE COURSE; DRUG ANTAGONISM; ENZYMOLOGY; FEMALE; HUMAN; METABOLISM; PATHOLOGY; REVIEW; SIGNAL TRANSDUCTION;

BREAST NEOPLASMS; DISEASE PROGRESSION; FEMALE; HUMANS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION;

EID: 34347269181     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/2367     Document Type: Article

References (85)

1. Cancer Facts & Figures, 2007 American Cancer Society
2. Bellacosa A, Testa JR, Staal SP & Tsichlis PN: A retroviral oncogene, Akt, encoding a serine-threonine kinase containing an SH2-like region. Science 254(5029):274-7 (1991) (Pubitemid 21917339)
3. Fresno Vara JA, Casado E, de Castro J, Cejas P, Beldainiesta C & Gonzalez-Baron M: PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 30(2):193-204 (2004)
4. Brazil DP, Yang ZZ & Hemmins BA: Advances in protein kinase B signaling: AKTion on multiple fronts. Trends Biochem Sci 29: (2004)
5. Zinda MJ, Johnson MA, Paul JD, Horn C, Konicek BW, Lu ZH, Sandusky G, Thomas JE, Neubauer BL, Lai MT & Graff JR: AKT-1,-2, and-3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon. Clin Cancer Res 7(8):2475-9 (2001) (Pubitemid 32751652)
6. Kada F, Saji M & Ringel MD: Akt: a potential target for thyroid cancer therapy. Curr Drug Targets Immune Endocr Metabol Disord. 4(3):181-5 (2004) (Pubitemid 39199356)
7. 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 13(2):137-44 (2006)
8. Klos KS, Zhou X, Lee S, Zhang L, Yang W, Nagata Y & Yu D: Combined trastuzumab and paclitaxel treatment better inhibits ErbB-2-mediated angiogenesis in breast carcinoma through a more effective inhibition of Akt than either treatment alone. Cancer 98(7):1377-1385 (2003) (Pubitemid 37151491)
9. Nakatani K, Thompson DA, Barthel A, Sakaue H, Liu W, Weigel RJ & Roth RA: Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgenindependent prostate cancer lines. J Biol Chem. 274(31):21528-32. (1999)
10. Jones PF, Jakubowicz T, Pitossi FJ, Maurer F & Hemmings BA: Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily. Proc Nal Acad Sci USA 88(10):4171-5 (1991) (Pubitemid 21914501)
11. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH & Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275(5308):1943-7 (1997) (Pubitemid 27148818)
12. Gao T, Furnari F & Newton AC: PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell 18(1):13-24 (2005) (Pubitemid 40444644)
13. Zhou BP, Liao Y, Xia W, Spohn B, Lee MH & Hung MC: Cytoplasmic localization of p21Cip1/WAF1 by Aktinduced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol 3(3):245-52 (2001) (Pubitemid 32201319)
14. Shin I, Yakes FM, Rojo F, Shin NY, Bakin AV, Baselga J & Arteaga CL: PKB/Akt mediates cell-cycle progression by phosphorylation of p27Kip1 at threonine 157 and modulation of its cellular localization. Nat Med 8(10):1145-52 (2002) (Pubitemid 35175970)
15. Hizli AA, Black AR, Pysz MA & Black JD: Protein kinase C-alpha signaling inhibits cyclin D1 translation in intestinal epithelial cells. J Biol Chem. 281(21):14596-603 (2006) (Pubitemid 43855163)
16. Cannings E, Kirkegaard T, Tovey SM, Dunne B, Cooke TG & Bartlett JM: Bad expression predicts outcome in patients treated with tamoxifen. Breast Cancer Res Treat (2006) DOI 10.1007/s10549-006-9323-8
17. Zhou BP, Hu MC, Miller SA, Yu Z, Xia W, Lin SY & Hung MC: HER-2/neu blocks tumor necrosis factorinduced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem. 275(11):8027-31 (2000) (Pubitemid 30159714)
18. Friedl P & Wolf K: Tumor-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3(5);362-74 (2003) (Pubitemid 37328856)
19. Shaw LM, Rabinovitz I, Wang HHF, Toker A, Mercurio AM: Activation of phosphoinositide 3-OH kinase by the alpha6beta4 integrin promotes carcinoma invasion. Cell 91: (1997)
20. Enomoto A, Murakami H, Asai N, Morone N, Watanabe T, Kawai K, Murakumo Y, Usukura J, Kaibuchi K & Takahashi M: Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev Cell 9(3):389-402 (2005) (Pubitemid 41235808)
21. Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN & Larue L: The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 63(9):2172-8 (2003) (Pubitemid 36538623)
22. Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M & Hung MC: Dual regulation of Snail by GSK-3betamediated phosphorylation in control of epithelialmesenchymal transition. Nat cell Bio 6(10):931-40 (2004) (Pubitemid 39359846)
23. Bonitsis N, Batistatou A, Karantima S & Charalabopoulos K: The role of cadherin/catenin complex in malignant melanoma. Exp Oncol. 28(3):187-93 (2006) (Pubitemid 44735907)
24. Brodbeck D, Hill MM & Hemmings BA: Two splice variants of protein kinase B gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site serine 472 in the carboxyl-terminal hydrophobic domain. J Biol Chem. 276(31):29550-8 (2001)
25. Brodbeck D, Cron P & Hemmings BA: A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain. J Biol Chem. 274(14):9133-6 (1999)
26. Chan TO, Rittenhouse SE & Tsichlis PN: AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide- dependent phosphorylation. Annu Rev Biochem. 68:965-1014 (1999) (Pubitemid 29449213)
27. Staal SP: Molecular cloning of the akt oncogene and its human homologues Akt1 and Akt2: amplification of Akt1 in a primary human gastric adenocarcinoma. Proc Nal Acad Sci USA 84(14):5034-7 (1987) (Pubitemid 17095859)
28. Cho, H., J. L. Thorvaldsen, Q. Chu, F. Feng, & M. J. Birnbaum. 2001b. Akt1/PKB-alpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J. Biol. Chem. 276:38349-38352.
29. Katome T, Obata T, Matsushima R, Masuyama N, Cantley LC, Gotoh Y, Kishi K, Shiota H & Ebina Y: Use of RNA interference-mediated gene silencing and adenoviral overexpression to elucidate the roles of AKT/protein kinase B isoforms in insulin actions. J Biol Chem. 278(30):28312-23 (2003) (Pubitemid 36900033)
30. Jauliac S, Lopez-Rodriguez C, Shaw LM, Brown LF, Rao A & Toker A: The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat Cell Biol 4(7):540-4 (2002) (Pubitemid 34752442)
31. Irie HY, Pearline RV, Grueneberg D, Hsia M, Ravichandran P, Kothari N, Natesan S & Brugge JS: Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. J Cell Biol 171(6):1023-34 (2005) (Pubitemid 41815834)
32. Okano, J. Gaslightwala, I., Brinbaum, M. J., Rustgi, A. K., & Nakagawa, H: Akt/protein kinase B isoforms are differentially regulated by epidermal growth factor sitmulation. J Biol Chem 275(40):30934-30942 (2000)
33. Yuan ZQ, Sun M, Feldman RI, Wang G, Ma X, Jiang C, Coppola D, Nicosia SV & Cheng JQ: Frequent activation of Akt2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer. Oncogene 19(19):2324-2330 (2000) (Pubitemid 30307208)
34. Zimmermann S & K Moelling: Phosphorylation and regulation of Raf by Akt (protein kinase B). Science 286: (1999)
35. Zhou BP, Liao Y, Xia W, Zou Y, Spohn B & Hung MC: Her-2/neu induces p53 ubiquitination via Aktmediated MDM2 phosphorylation. Nat Cell Biol 3(11):973-82 (2001) (Pubitemid 34428742)
36. Alex Alex Toker & Merav Yoeli-Lerner: Akt signaling and Cancer: Surviving but not moving on. Cancer Res. 66(8):3963-6 (2006)
37. Bellacosa, A., D. de Feo, A. K. Godwin, D. W. Bell, J. Q. Cheng, D. A. Altomare, M. Wan, L. Dubeau, G. Scambia & V. Masciullo: Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int. J. Cancer. 64:280-285 (1995)
38. Parsons, D. W., T. L. Wang, Y. Samuels, A. Bardelli, J. M. Cummins, L. DeLong, N. Silliman, J. Ptak, S. Szabo & J. K. Willson: Colorectal cancer: mutations in a signalling pathway. Nature. 436:792 (2005) (Pubitemid 41160630)
39. Maroulakou IG, Oemler W, Naber SP & Tsichlis PN: Akt1 ablation inhibits, whereas Akt2 ablation accelerates, the development of mammary adenocarcinomas in mouse mammary tumor virus (MMTV)-ErbB2/Neu and MMTV-Polyoma Middle T transgenic mice. Cancer Res 67(1):167-77 (2007) (Pubitemid 46142772)
40. Kurokawa H. & Arteaga CL: Inhibition of ErbB receptor (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer. Clin Cancer Res. 7:4436s-4442s (2001) (Pubitemid 34031593)
41. Dancey J & Sausville EA: Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev Drug Discov 2:296-313 (2003) (Pubitemid 37361688)
42. Bacus SS, Altomare DA, Lyass L, Chin DM, Farrel MP, Guroval K, Gudkov A. & Testa JR: Akt2 is frequently upregulated in HER-2/neu-positive breast cancers and may contribute to tumor aggressiveness by enhancing cell survival. Oncogene 21:3532-3540 (2002) (Pubitemid 34587685)
43. Sun M, Wang G, Paciga JE, Feldman RI, Yuan ZQ, Ma XL, Shelley SA, Jove R, Tsichlis PN, Nicosia SV & Cheng JQ: Akt1/PKB-alpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. American Journal of Pathology 159(2):431-7 (2001) (Pubitemid 32751073)
44. Stal O, Perez-Tenorio G, Akerberg L, Olsson B, Nordenskjold B, Skoog L & Rutqvist LE: Akt kinases in breast cancer and the results of adjuvant therapy. Breast cancer research 5(2):R37-R44 (2003)
45. Duong BN, Elliott S, Frigo DE, Melnik LI, Vanhoy L, Tomchuck S, Lebeau HP, David O, Beckman BS, Alam J, Bratton MR, McLachlan JA & Burow ME: Akt regulation of estrogen receptorbeta transcriptional activity in breast cancer Cancer Res. 66(17):8373-81 (2006) (Pubitemid 44449147)
46. 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 ErbB 2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Research 65(7):2554-9 (2005) (Pubitemid 40490050)
47. Nicholson KM & Anderson NG: The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14(5):381-395 (2002) (Pubitemid 34214843)
48. Shoman N, Klassen S, McFadden A, Bickis MG, Torlakovic E & Chibbar R: Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. Mod Pahol. 18(2):250-259 (2005) (Pubitemid 40188633)
49. Xia W, Chen JS, Zhou X, Sun PR, Lee DF, Liao Y, Zhou BP & Hung MC: Phosphorylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients. Clin Cancer Res. 10(11):3815-3824 (2004) (Pubitemid 38697617)
50. 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 over-expression predicts tumor progression in breast cancers. Clinical Cancer Research 10(9):6779-6788 (2004) (Pubitemid 39383026)
51. Tan Y, Ruan H, Demeter MR. & Comb MJ: p90(RSK) blocks bad-mediated cell death via a protein kinase C-dependent pathway. J. Biol Chem 274 (49):34859-67 (1999) (Pubitemid 129509532)
52. Harada H, Andersen JS, Mann M, Terada N & Korsmeyer SJ: p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc Natl Acad Sci USA 98(17):9666-70 (2001) (Pubitemid 32769360)
53. Menendez JA, Mehmi I, Verma VA, Teng PK & Lupu R: Pharmacological inhibition of Fatty Acid Synthase FAS: a novel therapeutic approach for breast cancer chemoprevention through its ability to suppress Her-2/neu erbB-2 oncogene-induced malignant transformation. Mol Carcinog 41(3):164-178 (2004) (Pubitemid 39435113)
54. Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D, Vinci F, Chiappetta G, Tsichlis P, Bellacosa A, Fusco A & Santoro M: Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27Kip1 by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 8(10):1136-44 (2002) (Pubitemid 35175969)
55. Vasko V, Saji M, Hardy E, Kruhlak M, Larin A, Savchenko V, Miyakawa M, Isozaki O, Murakami H, Tsushima T, Burman KD, De Micco C & Ringel MD: Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer. J Med Genet, 41(3):161-170 (2002) (Pubitemid 38333792)
56. Martin MB, Franke TF, Stoica GE, Chambon P, Katzenellenbogen BS, Stoica BA, McLemore MS, Olivo SE & Stoica A: A role for Akt in mediating the estrogenic functions of epidermal growth factor and insulin-like growth factor I. Endocrinology 141(12):4503-11 (2000) (Pubitemid 32055127)
57. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S & Nakshatri H: Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 276(13):9817-24 (2001)
58. Speirs V, Carder PJ, Lane S, Dodwell D, Lansdown MR & Hanby AM: Oestrogen receptorbeta: what it means for patients with breast cancer. Lancet Oncol 5(3):174-81 (2004) (Pubitemid 38262850)
59. Coronato S, Laguens GE, Spinelli OM & Di Girolamo W: Tumor markers in breast neoplasm. Medicina (B Aires) 62(1):73-82 (2002)
60. Osborne CK: Tamoxifen in the treatment of breast cancer. N Engl J Med, 339(22):1609-18 (1998) (Pubitemid 28536137)
61. Perez-Tenorio G, Stal O & Southeast Sweden Breast Cancer Group: Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 86(4):540-5 (2002) (Pubitemid 34185089)
62. Johnston SR: Combinations of endocrine and biological agents: present status of therapeutic and presurgical investigations. Clin Cancer Res, 11:889s-899s (2005) (Pubitemid 40111102)
63. Barnett SF, Bilodeau MT & Lindsley CW: The Akt/PKB Family of Protein Kinases: A review of small molecule inhibitors and progress towards target validation. Current Topics in Medicinal Chemistry 5(2):109-25 (2005) (Pubitemid 40514509)
64. Garcia-Echeverria C, Traxler P & Evans DB: ATP sitedirected competitive and irreversible inhibitors of protein kinases. Med Res Rev 20(1):28-57 (2000) (Pubitemid 30027560)
65. Amarvadi R & Thompson CB: The survival kinases Akt and Pim as potential pharmacological targets. J. Clin. Invest. 115(10):2618-24 (2005) (Pubitemid 41434384)
66. Cheng JQ, Lindsley CW, Cheng GZ, Yang H & Nicosia SV: The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene 24(50):7482-92 (2005) (Pubitemid 41637988)
67. Dimmeler, S & Zeiher, AM: Akt takes center stage in angiogenesis signaling. Circ. Res. 86(1):4-5 (2000) (Pubitemid 30044160)
68. Fukumura, D. Gohongi, T. Kadambi, A. Izumi, Y., Ang, J. Yun, C. O. Buerk, D. G., Huang, P. L. & Jain, R. K: Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. Proc. Natl. Acad. Sci. USA 98(5):2604-2609 (2001) (Pubitemid 32209529)
69. Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K & Franke TF, Papapetropoulos A, Sessa WC: Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399(6736):597-601 (1999)
70. Phung TL, Ziv K, Dabydeen D, Eyiah-Mensah G, Riveros M, Perruzzi C, Sun J, Monahan-Earley RA, Shiojima I, Nagy JA, Lin MI, Walsh K, Dvorak AM, Briscoe DM, Neeman M, Sessa WC, Dvorak HF & Benjamin LE: Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin Cancer Cell. 10(2):159-70 (2006) (Pubitemid 44175906)
71. Blommaart EF, Luiken JJ, Blommaart PJ, van Woerkom GM & Meijer AJ: Phosphorlation of ribosomal protein S6 is inhibitory for autophage in isolated rat hepatocytes. J Biol Chem 270(5):2320-6 (1995)
72. Edinger AL & Thompson CB: Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Bio Cell 13(7):2276-88 (2002) (Pubitemid 34831333)
73. Lenka Dubaska, Ladislav Andera & Michael Allen Sheard: HER2 signaling downregulation by trastuzumab and suppression of the PI3K/Akt patghway: An unexpected effect on TRAIL-induced apoptosis. FEBS lett. 579(19);4149-4158 (2005) (Pubitemid 41021805)
74. Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA & Slamon DJ: Phase II study of receptorenhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16(8):2659-2671 (1998) (Pubitemid 28363029)
75. Lee S, Yang W, Lan KH, Sellappan S, Klos K, Hortobagyi G, Hung MC & Yu D: Enhanced sensitization to taxol-induced apoptosis by herceptin pretreatment in ErbB2-overexpressing breast cancer cells. Cancer Res 62(20):5703-10 (2002) (Pubitemid 35204725)
76. Tokunaga E, Kimura Y, Oki E, Ueda N, Futatsugi M, Mashino K, Yamamoto M, Ikebe M, Kakeji Y, Baba H & Maehara Y: Akt is frequently activated in HER2/neupositive breast cancers and associated with poor prognosis among hormone-treated patients. Int J Cancer. 118(2):284-9 (2006) (Pubitemid 41779066)
77. Ueda S, Tsuda H, Sato K, Takeuchi H, Shigekawa T, Matsubara O, Hiraide H & Mochizuki H: Alternative tyrosine phosphorylation of signaling kinases according to hormone receptor status in breast cancer overexpressing the insulin-like growth factor receptor type I. Cancer Sci. 97(7):597-604 (2006) (Pubitemid 44056607)
78. Sahoo S, Brickley DR, Kocherginsky M & Conzen SD: Coordinate expression of the PI3-kinase downstream effectors serum and glucocorticoid- induced kinase (SGK-1) and Akt-1 in human breast cancer. Eur J Cancer. 41(17):2754-9 (2005) (Pubitemid 41607569)
79. Schmitz KJ, Otterbach F, Callies R, Levkau B, Holscher M, Hoffmann O, Grabellus F, Kimmig R, Schmid KW & Baba HA: Prognostic relevance of activated Akt kinase in node-negative breast cancer: a clinicopathological study of 99 cases. Mod Pathol. 17(1):15-21 (2004) (Pubitemid 41656447)
80. Kirkegaard T, Witton CJ, McGlynn LM, Tovey SM, Dunne B, Lyon A & Bartlett JM: Akt activation predicts outcome in breast cancer patients treated with tamoxifen J. of Pathology 207(2):139-146 (2005) (Pubitemid 41404144)
81. Guertin DA & Sabatini DM: An expanding role for mTOR in cancer. Trends Mol. Med. 11, 353-361 (2005) (Pubitemid 41080576)
82. Panigrahi AR, Pinder SE, Chan SY, Paish EC, Robertson JF & Ellis IO: The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome. J. Pathology 204(1):93-100 (2004) (Pubitemid 39214486)
83. Lin HJ, Hsieh FC, Song H & Lin J: Elevated phosphorylation and activation of PDK-1/AKT pathway in human breast cancer. Br J Cancer 93(12):1372-81 (2005) (Pubitemid 41752864)
84. Bose S, Chandran S, Mirocha JM & Bose N: The Akt pathway in human breast cancer: a tissue-array-based analysis. Mod Pathol. 19(2), 238-45 (2006) (Pubitemid 43117608)
85. Shi W, Zhang X, Pintilie M, Ma N, Miller N, Banerjee D, Tsao MS, Mak T, Fyles A & Liu FF: Dysregulated PTEN-PKB and negative receptor status in human breast cancer. Int J Cancer. 104(2):195-203 (2003) (Pubitemid 36249795)