Photo of Peter Sicinski,  MD, PhD

Peter Sicinski, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-5005
Fax: (617) 632-5006

Peter Sicinski, MD, PhD

Dana-Farber Cancer Institute


  • Professor, Genetics, Harvard Medical School


Research Abstract

The proliferation of mammalian cells is tightly controlled by numerous external signals. After they are received by the cells, these growth-promoting or growth-inhibitory signals are transmitted to the so-called cell-cycle machinery operating in the nucleus. The cell-cycle machinery is present in every single cell, and it can be thought of as the molecular engine that drives cell proliferation. The key components of this machinery are proteins termed cyclins. Abnormal expression of cyclins is seen in a great number of human cancers. For example, more than 50% of human breast cancers contain highly elevated levels of a particular cyclin protein, termed cyclin D1. Importantly, because agents that antagonize this cyclin have been shown to shut off the proliferation of breast cancer cells grown in vitro, overexpression of cyclin D1 seems to play a causative role in mammary tumorigenesis.

To understand the role played by these various cyclin proteins in normal development and in cancer, we generated several genetically engineered 'knockout' mouse strains lacking different cyclin proteins. We found that each of these proteins is required for proliferation in a very narrow, highly specific sets of tissues. For example, we discovered that cyclin D1-deficient mice develop hormone-insensitive mammary glands. Hence, the normal, physiologic role for cyclin D1 is to drive hormone-induced mammary epithelial proliferation, while overexpression of the very same cyclin plays a causative role in human breast cancers.

We are currently using these knockout strains, and cells derived from them, as tools to study the role of particular cyclin proteins in normal cell proliferation and in oncogenesis of breast cancers, in particular. Moreover, we are generating novel mutant mouse strains that will help explain the role of cell-cycle machinery at the organismal, cellular, and molecular levels.


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  • Li N, Fassl A, Chick J, Inuzuka H, Li X, Mansour MR, Liu L, Wang H, King B, Shaik S, Gutierrez A, Ordureau A, Otto T, Kreslavsky T, Baitsch L, Bury L, Meyer CA, Ke N, Mulry KA, Kluk MJ, Roy M, Kim S, Zhang X, Geng Y, Zagozdzon A, Jenkinson S, Gale RE, Linch DC, Zhao JJ, Mullighan CG, Harper JW, Aster JC, Aifantis I, von Boehmer H, Gygi SP, Wei W, Look AT, Sicinski P. Cyclin C is a haploinsufficient tumour suppressor. Nat Cell Biol 2014; 16:1080-91. PubMed
  • Bhalla K, Liu WJ, Thompson K, Anders L, Devarakonda S, Dewi R, Buckley S, Hwang BJ, Polster B, Dorsey SG, Sun Y, Sicinski P, Girnun GD. Cyclin D1 Represses Gluconeogenesis via Inhibition of the Transcriptional Coactivator PGC1留. Diabetes 2014; 63:3266-78. PubMed
  • Choi YJ, Saez B, Anders L, Hydbring P, Stefano J, Bacon NA, Cook C, Kalaszczynska I, Signoretti S, Young RA, Scadden DT, Sicinski P. D-cyclins repress apoptosis in hematopoietic cells by controlling death receptor Fas and its ligand FasL. Dev Cell 2014; 30:255-67. PubMed
  • Lee Y, Dominy JE, Choi YJ, Jurczak M, Tolliday N, Camporez JP, Chim H, Lim JH, Ruan HB, Yang X, Vazquez F, Sicinski P, Shulman GI, Puigserver P. Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle progression. Nature 2014. PubMed
  • Naetar N, Soundarapandian V, Litovchick L, Goguen KL, Sablina AA, Bowman-Colin C, Sicinski P, Hahn WC, DeCaprio JA, Livingston DM. PP2A-Mediated Regulation of Ras Signaling in G2 Is Essential for Stable Quiescence and Normal G1 Length. Mol Cell 2014. PubMed
  • Liu P, Begley M, Michowski W, Inuzuka H, Ginzberg M, Gao D, Tsou P, Gan W, Papa A, Kim BM, Wan L, Singh A, Zhai B, Yuan M, Wang Z, Gygi SP, Lee TH, Lu KP, Toker A, Pandolfi PP, Asara JM, Kirschner MW, Sicinski P, Cantley L, Wei W. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature 2014; 508:541-5. PubMed
  • Martinerie L, Manterola M, Chung SS, Panigrahi SK, Weisbach M, Vasileva A, Geng Y, Sicinski P, Wolgemuth DJ. Mammalian E-type cyclins control chromosome pairing, telomere stability and CDK2 localization in male meiosis. PLoS Genet. 2014; 10:e1004165. PubMed
  • Narasimha AM, Kaulich M, Shapiro GS, Choi YJ, Sicinski P, Dowdy SF. Cyclin D activates the Rb tumor suppressor by mono-phosphorylation. Elife 2014. PubMed
  • Geng Y, Sicinski P. Differences in regulation and function of E-cyclins in human cancer cells. Cell Cycle 2013; 12:1165. PubMed
  • Cho KH, Sicinski P. Unexpected outcomes of CDK4/6 inhibition. 2013; 4:176-7. PubMed
  • Nakaya T, Ishiguro KI, Belzil C, Rietsch AM, Yu Q, Mizuno SI, Bronson RT, Geng Y, Nguyen MD, Akashi K, Sicinski P, Nakatani Y. p600 Plays Essential Roles in Fetal Development. PLoS ONE 2013; 8:e66269. PubMed
  • Kreslavsky T, Gleimer M, Miyazaki M, Choi Y, Gagnon E, Murre C, Sicinski P, von Boehmer H. 硫-Selection-Induced Proliferation Is Required for 留硫 T Cell Differentiation. Immunity 2012; 37:840-53. PubMed
  • Chen HZ, Ouseph MM, Li J, Pécot T, Chokshi V, Kent L, Bae S, Byrne M, Duran C, Comstock G, Trikha P, Mair M, Senapati S, Martin CK, Gandhi S, Wilson N, Liu B, Huang YW, Thompson JC, Raman S, Singh S, Leone M, Machiraju R, Huang K, Mo X, Fernandez S, Kalaszczynska I, Wolgemuth DJ, Sicinski P, Huang T, Jin V, Leone G. Canonical and atypical E2Fs regulate the mammalian endocycle. Nat Cell Biol 2012; 14:1192-202. PubMed
  • Choi YJ, Li X, Hydbring P, Sanda T, Stefano J, Christie AL, Signoretti S, Look AT, Kung AL, von Boehmer H, Sicinski P. The requirement for cyclin D function in tumor maintenance. Cancer Cell 2012; 22:438-51. PubMed
  • Sankaran VG, Ludwig LS, Sicinska E, Xu J, Bauer DE, Eng JC, Patterson HC, Metcalf RA, Natkunam Y, Orkin SH, Sicinski P, Lander ES, Lodish HF. Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number. Genes Dev 2012; 26:2075-87. PubMed
  • Jirawatnotai S, Hu Y, Livingston DM, Sicinski P. Proteomic identification of a direct role for cyclin d1 in DNA damage repair. Cancer Res 2012; 72:4289-93. PubMed
  • Odajima J, Kalaszczynska I, Sicinski P. Cyclins A and E trigger DNA damage. Cell Cycle 2010; 9:1231-2. PubMed
  • Cole AM, Myant K, Reed KR, Ridgway RA, Athineos D, Van den Brink GR, Muncan V, Clevers H, Clarke AR, Sicinski P, Sansom OJ. Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc loss. Cancer Res 2010; 70:8149-58. PubMed
  • Peled JU, Yu JJ, Venkatesh J, Bi E, Ding BB, Krupski-Downs M, Shaknovich R, Sicinski P, Diamond B, Scharff MD, Ye BH. Requirement for cyclin D3 in germinal center formation and function. Cell Res 2010; 20:631-46. PubMed
  • Bienvenu F, Jirawatnotai S, Elias JE, Meyer CA, Mizeracka K, Marson A, Frampton GM, Cole MF, Odom DT, Odajima J, Geng Y, Zagozdzon A, Jecrois M, Young RA, Liu XS, Cepko CL, Gygi SP, Sicinski P. Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature 2010; 463:374-8. PubMed
  • Nevzorova YA,Tschaharganeh D,Gassler N,Geng Y,Weiskirchen R,Sicinski P,Trautwein C,Liedtke C. Aberrant Cell Cycle Progression and Endoreplication in Regenerating Livers of Mice That Lack a Single E-Type Cyclin. Gastroenterology 2009; 137:691-703, 703.e1-6. PubMed
  • Kalaszczynska I, Geng Y, Iino T, Mizuno S, Choi Y, Kondratiuk I, Silver DP, Wolgemuth DJ, Akashi K, Sicinski P. Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells. Cell 2009; 138:352-65. PubMed
  • Francis RE, Myatt SS, Krol J, Hartman J, Peck B, McGovern UB, Wang J, Guest SK, Filipovic A, Gojis O, Palmieri C, Peston D, Shousha S, Yu Q, Sicinski P, Coombes RC, Lam EW. FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer. Int J Oncol 2009; 35:57-68. PubMed
  • Joshi I,Minter LM,Telfer J,Demarest RM,Capobianco AJ,Aster JC,Sicinski P,Fauq A,Golde TE,Osborne BA. Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood 2008; 113:1689-98. PubMed
  • Zeng L,Geng Y,Tretiakova M,Yu X,Sicinski P,Kroll TG. Peroxisome proliferator-activated receptor-delta induces cell proliferation by a cyclin E1-dependent mechanism and is up-regulated in thyroid tumors. Cancer Res 2008; 68:6578-86. PubMed
  • Landis MW, Brown NE, Baker GL, Shifrin A, Das M, Geng Y, Sicinski P, Hinds PW. The LxCxE pRb interaction domain of cyclin D1 is dispensable for murine development. Cancer Res 2007; 67:7613-20. PubMed
  • Sicinski P, Zacharek S, Kim C. Duality of p27Kip1 function in tumorigenesis. Genes Dev 2007; 21:1703-6. PubMed
  • Geng Y, Lee YM, Welcker M, Swanger J, Zagozdzon A, Winer JD, Roberts JM, Kaldis P, Clurman BE, Sicinski P. Kinase-independent function of cyclin E. Mol Cell 2007; 25:127-39. PubMed
  • Sicinska E, Lee YM, Gits J, Shigematsu H, Yu Q, Rebel VI, Geng Y, Marshall CJ, Akashi K, Dorfman DM, Touw IP, Sicinski P. Essential role for cyclin D3 in granulocyte colony-stimulating factor-driven expansion of neutrophil granulocytes. Mol Cell Biol 2006; 26:8052-60. PubMed
  • Lee YM, Sicinski P. Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. Cell Cycle 2006; 5:2110-4. PubMed
  • Cooper AB, Sawai CM, Sicinska E, Powers SE, Sicinski P, Clark MR, Aifantis I. A unique function for cyclin D3 in early B cell development. Nat Immunol 2006; 7:489-97. PubMed
  • Isaac CE, Francis SM, Martens AL, Julian LM, Seifried LA, Erdmann N, Binn. The retinoblastoma protein regulates pericentric heterochromatin. Mol Cell Biol 2006; 26:3659-71. PubMed
  • Landis MW, Pawlyk BS, Li T, Sicinski P, Hinds PW. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell 2006; 9:13-22. PubMed
  • Yu Q, Sicinska E, Geng Y, Ahnstr. Requirement for CDK4 kinase function in breast cancer. Cancer Cell 2006; 9:23-32. PubMed
  • Yu Q, Ciemerych MA, Sicinski P. Ras and Myc can drive oncogenic cell proliferation through individual D-cyclins. Oncogene 2005; 24:7114-9. PubMed
  • Kushner JA, Ciemerych MA, Sicinska E, Wartschow LM, Teta M, Long SY, Sicinski P, White MF. Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth. Mol Cell Biol 2005; 25:3752-62. PubMed
  • Deshpande A, Sicinski P, Hinds PW. Cyclins and cdks in development and cancer: a perspective. Oncogene 2005; 24:2909-15. PubMed
  • Ciemerych MA, Sicinski P. Cell cycle in mouse development. Oncogene 2005; 24:2877-98. PubMed
  • Kozar K, Sicinski P. Cell cycle progression without cyclin D-CDK4 and cyclin D-CDK6 complexes. Cell Cycle 2005; 4:388-91. PubMed
  • Carthon BC, Neumann CA, Das M, Pawlyk B, Li T, Geng Y, Sicinski P. Genetic replacement of cyclin D1 function in mouse development by cyclin D2. Mol Cell Biol 2005; 25:1081-8. PubMed
  • Kowalczyk A, Filipkowski RK, Rylski M, Wilczynski GM, Konopacki FA, Jaworski J, Ciemerych MA, Sicinski P, Kaczmarek L. The critical role of cyclin D2 in adult neurogenesis. J Cell Biol 2004; 167:209-13. PubMed
  • Kozar K, Ciemerych MA, Rebel VI, Shigematsu H, Zagozdzon A, Sicinska E, Geng Y, Yu Q, Bhattacharya S, Bronson RT, Akashi K, Sicinski P. Mouse development and cell proliferation in the absence of D-cyclins. Cell 2004; 118:477-91. PubMed
  • Geng Y, Yu Q, Sicinska E, Das M, Schneider JE, Bhattacharya S, Rideout WM, Bronson RT, Gardner H, Sicinski P. Cyclin E ablation in the mouse. Cell 2003; 114:431-43. PubMed
  • Ciemerych MA, Kenney AM, Sicinska E, Kalaszczynska I, Bronson RT, Rowitch DH, Gardner H, Sicinski P. Development of mice expressing a single D-type cyclin. Genes Dev 2002; 16:3277-89. PubMed
  • Jena N, Deng M, Sicinska E, Sicinski P, Daley GQ. Critical role for cyclin D2 in BCR/ABL-induced proliferation of hematopoietic cells. Cancer Res 2002; 62:535-41. PubMed
  • Geng Y, Yu Q, Whoriskey W, Dick F, Tsai KY, Ford HL, Biswas DK, Pardee AB, Amati B, Jacks T, Richardson A, Dyson N, Sicinski P. Expression of cyclins E1 and E2 during mouse development and in neoplasia. Proc Natl Acad Sci U S A 2001; 98:13138-43. PubMed
  • Yu Q, Geng Y, Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature 2001; 411:1017-21. PubMed
  • Geng Y, Yu Q, Sicinska E, Das M, Bronson RT, Sicinski P. Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice. Proc Natl Acad Sci U S A 2001; 98:194-9. PubMed
  • Kim HA, Pomeroy SL, Whoriskey W, Pawlitzky I, Benowitz LI, Sicinski P, Stiles CD, Roberts TM. A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1. Neuron 2000; 26:405-16. PubMed
  • Geng Y, Whoriskey W, Park MY, Bronson RT, Medema RH, Li T, Weinberg RA, Sicinski P. Rescue of cyclin D1 deficiency by knockin cyclin E. Cell 1999; 97:767-77. PubMed
  • Robles AI, Rodriguez-Puebla ML, Glick AB, Trempus C, Hansen L, Sicinski P, Tennant RW, Weinberg RA, Yuspa SH, Conti CJ. Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo. Genes Dev 1998; 12:2469-74. PubMed
  • Sicinski P, Weinberg RA. A specific role for cyclin D1 in mammary gland development. J Mammary Gland Biol Neoplasia 2000; 2:335-42. PubMed
  • Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner H, Park MY, Robker RL, Richards JS, McGinnis LK, Biggers JD, Eppig JJ, Bronson RT, Elledge SJ, Weinberg RA. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature 1996; 384:470-4. PubMed
  • Wang Z, Sicinski P, Weinberg RA, Zhang Y, Ravid K. Characterization of the mouse cyclin D3 gene: exon/intron organization and promoter activity. Genomics 1996; 35:156-63. PubMed
  • Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ, Weinberg RA. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 1995; 82:621-30. PubMed
  • Geng Y, Sicinski P, Gorecki D, Barnard PJ. Developmental and tissue-specific regulation of mouse dystrophin: the embryonic isoform in muscular dystrophy. Neuromuscul Disord 1991; 1:125-33. PubMed
  • Sicinski P, Rowinski J, Warchol JB, Jarzabek Z, Gut W, Szczygiel B, Bielecki K, Koch G. Poliovirus type 1 enters the human host through intestinal M cells. Gastroenterology 1990; 98:56-8. PubMed
  • Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 1989; 244:1578-80. PubMed
  • Ryder-Cook AS, Sicinski P, Thomas K, Davies KE, Worton RG, Barnard EA, Darlison MG, Barnard PJ. Localization of the mdx mutation within the mouse dystrophin gene. EMBO J 1988; 7:3017-21. PubMed
  • Rell KW, Lamprecht J, Sicinski P, Bem W, Rowinski J. Frequency of occurrence and distribution of the intra-epithelial lymphoid cells in the follicle-associated epithelium in phenotypically normal and athymic nude mice. J Anat 1987; 152:121-31. PubMed
  • Sicinski P, Rowinski J, Warchol JB, Bem W. Morphometric evidence against lymphocyte-induced differentiation of M cells from absorptive cells in mouse Peyer's patches. Gastroenterology 1986; 90:609-16. PubMed
  • Rowinski J, Lamprecht J, Sicinski P. Non-random distribution of intraepithelial lymphoid cells in follicle-associated epithelium of Peyer's patches in mice. J Anat 1984; 139 ( Pt 1):21-32. PubMed
  • Sicinski P, Rowinski J, Warchol J. Intracisternal granules in the intestinal absorptive cells in mice. Cell Biol Int Rep 1984; 8:499-506. PubMed