| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 16, 2002
Accepted on July 24, 2003
1 Instituto de Investigaciones Biomédicas, C.S.I.C., Calle Arturo Duperier, 4; 28029 Madrid (Spain), Istituto Superiore di Sanitá, Viale Regina Elena, 299; 00161 Rome (Italy), Centro de Investigaciones Biológicas, C.S.I.C., Calle Velásquez 144; 28006 Madrid
* To whom correspondence should be addressed. E-mail: jmartin{at}iib.uam.es.
PRL (PRL) stimulates breast cancer cell proliferation, however, the involvement of PRL-activated signaling molecules in cell proliferation is not fully established. Here we studied the role of c-Src on PRL-stimulated proliferation of T47D and MCF7 breast cancer cells. We initially observed that PRL-dependent activation of Fak, Erk1/2 and cell proliferation was mediated by c-Src in T47D cells, because expression of a dominant-negative form of c-Src (SrcDM, K295A/Y527F) blocked the PRL-dependent effects. The Src inhibitor PP1 abrogated PRL-dependent in vivo activation of Fak, Erk1/2, p70S6K, Akt and the proliferation of T47D and MCF7 cells; Jak2 activation was not affected. However, in vitro, Fak and Jak2 kinases were not directly inhibited by PP1, demonstrating the effect of PP1 on c-Src kinase as an upstream activator of Fak.Expression of Fak mutant Y397F abrogated PRL-dependent activation of Fak, Erk1/2 and thymidine incorporation, but had no effect on p70S6K and Akt kinases. Mek1/2 inhibitor PD184352 blocked PRL-induced stimulation of Erk1/2 and cell proliferation, however, p70S6K and Akt activation were unaffected. The PI3K inhibitor LY294002 abolished cell proliferation and activation of p70S6K and Akt, however, PRL-dependent activation of Erk1/2 was not modified. Moreover, we show that both c-Src/PI3K and c-Src/Fak/Erk1/2 pathways are involved in the up-regulation of c-myc and cyclin d1 expression mediated by PRL. The previous findings suggest the existence of two PRL-dependent signaling cascades, initiated by the c-Src-mediated activation of Fak/Erk1/2 and PI3K pathways that, subsequently, control the expression of c-Myc and cyclin D1 and the proliferation of T47D and MCF7 breast cancer cells.
This article has been cited by other articles:
 |
|
 |
|
  R. S. Muraoka-Cook, M. Sandahl, D. Hunter, L. Miraglia, and H. S. Earp III Prolactin and ErbB4/HER4 Signaling Interact via Janus Kinase 2 to Induce Mammary Epithelial Cell Gene Expression Differentiation Mol. Endocrinol., October 1, 2008; 22(10): 2307 - 2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Neilson, J. Zhu, J. Xie, M. G. Malabarba, K. Sakamoto, K.-U. Wagner, R. A. Kirken, and H. Rui Coactivation of Janus Tyrosine Kinase (Jak)1 Positively Modulates Prolactin-Jak2 Signaling in Breast Cancer: Recruitment of ERK and Signal Transducer and Activator of Transcription (Stat)3 and Enhancement of Akt and Stat5a/b Pathways Mol. Endocrinol., September 1, 2007; 21(9): 2218 - 2232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sakamoto, B. A. Creamer, A. A. Triplett, and K.-U. Wagner The Janus Kinase 2 Is Required for Expression and Nuclear Accumulation of Cyclin D1 in Proliferating Mammary Epithelial Cells Mol. Endocrinol., August 1, 2007; 21(8): 1877 - 1892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Doll, J. Pfeilschifter, and A. Huwiler Prolactin upregulates sphingosine kinase-1 expression and activity in the human breast cancer cell line MCF7 and triggers enhanced proliferation and migration Endocr. Relat. Cancer, June 1, 2007; 14(2): 325 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Thamilselvan, D. H. Craig, and M. D. Basson FAK association with multiple signal proteins mediates pressure-induced colon cancer cell adhesion via a Src-dependent PI3K/Akt pathway FASEB J, June 1, 2007; 21(8): 1730 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Polgar, B. Fogelgren, J. M. Shipley, and K. Csiszar Lysyl Oxidase Interacts with Hormone Placental Lactogen and Synergistically Promotes Breast Epithelial Cell Proliferation and Migration J. Biol. Chem., February 2, 2007; 282(5): 3262 - 3272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Gadd and C. V. Clevenger Ligand-Independent Dimerization of the Human Prolactin Receptor Isoforms: Functional Implications Mol. Endocrinol., November 1, 2006; 20(11): 2734 - 2746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D Bishop, W. L. Nien, S. M Dauphinee, and C. K L Too Prolactin activates mammalian target-of-rapamycin through phosphatidylinositol 3-kinase and stimulates phosphorylation of p70S6K and 4E-binding protein-1 in lymphoma cells. J. Endocrinol., August 1, 2006; 190(2): 307 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gonzalez, M. T. Agullo-Ortuno, J. M. Garcia-Martinez, A. Calcabrini, C. Gamallo, J. Palacios, A. Aranda, and J. Martin-Perez Role of c-Src in Human MCF7 Breast Cancer Cell Tumorigenesis J. Biol. Chem., July 28, 2006; 281(30): 20851 - 20864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Srirangam, R. Mitra, M. Wang, J. C. Gorski, S. Badve, L. Baldridge, J. Hamilton, H. Kishimoto, J. Hawes, L. Li, et al. Effects of HIV Protease Inhibitor Ritonavir on Akt-Regulated Cell Proliferation in Breast Cancer Clin. Cancer Res., March 15, 2006; 12(6): 1883 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Nouhi, N. Chughtai, S. Hartley, E. Cocolakis, J.-J. Lebrun, and S. Ali Defining the Role of Prolactin as an Invasion Suppressor Hormone in Breast Cancer Cells Cancer Res., February 1, 2006; 66(3): 1824 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Neron, G. Suck, X.-Z. Ma, D. Sakac, A. Roy, Y. Katsman, N. Dussault, C. Racine, and D. R. Branch B cell proliferation following CD40 stimulation results in the expression and activation of Src protein tyrosine kinase Int. Immunol., February 1, 2006; 18(2): 375 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Jackson, L. Gao, and C. Zhu Mechanism of the Vascular Angiotensin II/{alpha}2-Adrenoceptor Interaction J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1109 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Gutzman, D. E. Rugowski, M. D. Schroeder, J. J. Watters, and L. A. Schuler Multiple Kinase Cascades Mediate Prolactin Signals to Activating Protein-1 in Breast Cancer Cells Mol. Endocrinol., December 1, 2004; 18(12): 3064 - 3075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cui, G. Riedlinger, K. Miyoshi, W. Tang, C. Li, C.-X. Deng, G. W. Robinson, and L. Hennighausen Inactivation of Stat5 in Mouse Mammary Epithelium during Pregnancy Reveals Distinct Functions in Cell Proliferation, Survival, and Differentiation Mol. Cell. Biol., September 15, 2004; 24(18): 8037 - 8047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad, A. Z. Fernandis, Y. Rao, and R. K. Ganju Slit Protein-mediated Inhibition of CXCR4-induced Chemotactic and Chemoinvasive Signaling Pathways in Breast Cancer Cells J. Biol. Chem., March 5, 2004; 279(10): 9115 - 9124. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
