|
|
Exogenous 17β-estradiol promote the invasion and proliferation of HER2 positive breast cancer cells |
XU Baobao1, JIANG Yang1,2, WANG Jindan1, LI Xiqi1, HE Yuanyuan1, RUAN Qingqing1, LIU Pengcheng1, GAO Guohui1, JIN Longjin1 |
1.Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035; 2.Department of Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035
|
|
Cite this article: |
XU Baobao,JIANG Yang,WANG Jindan, et al. Exogenous 17β-estradiol promote the invasion and proliferation of HER2 positive breast cancer cells [J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2017, 47(5): 329-335.
|
|
Abstract Objective: To investigate the correlation between exogenous estrogens (EEs) and the development risk of HER2 positive breast cancer cells. Methods: We treated HER2-positive and ERα-negative cells SKBR3, ERα-positive and HER2-negative cells MCF-7 with 17β-estradiol. The six different concentrations of 17β-estradiol were 10-5, 10-6, 10-7, 10-8, 10-9, 10-10 mol/L. For each concentration condition, there were three time dose such as 24 h, 48 h, 72 h. The expression levels of HER2 and ERα were observed as the key positive marker. And then cell invasion and cell proliferation of breast cancer cells were analysed for MCF-7 and SKBR3 under 17β-estradiol treatment. Results: It showed that the transcriptional levels of HER2 and ERα were upregulated in MCF7 cells under all 18 different conditions. However, only the transcriptional levels of HER2 was upregulated in all 18 different conditions in HER2-positive and ERα-negative SKBR3. At protein expression levels, HER2 in SKBR3 cells and ERα in MCF-7 cells were expressed apparently after the breast cancer cells were stimulated by 17β-estradiol under all different conditions. Simultaneously,the proliferation of MCF-7 and SKBR3 were promoted obviously. With the higher concentration of 17β-estradiol treatment the proliferative activity of these two breast cancer cells were promoted much more obviously. As for the invasion of the breast cancer cells, MCF-7 was increased after 72 h, and SKBR3 was increased after 24 h and 48 h. Whereas the invasion of SKBR3 and MCF-7 were not up or down regulated evidently with the change of concentrations and time. Conclusion: In a word, the expression levels of HER2 in HER2 positive breast cancer cells SKBR3 are upregulated under different 17β-estradiol treatment conditions. Furthermore, the invasion and proliferation of HER2 positive breast cancer cells SKBR3 are promoted under exogenous estrogens 17β-estradiol treatment.
|
Received: 19 September 2016
|
|
|
|
|
[1] TOVEY S M, REEVES J R, STANTON P, et al. Low expression of HER2 protein in breast cancer is biologically significant[J]. J Pathol, 2006, 210(3): 358-362.
[2] LANDIS M D, SEACHRIST D D, ABDUL-KARIM F W, et al. Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors[J]. Oncogene, 2006, 25(23): 3325-3334.
[3] KEY T, APPLEBY P, BARNES I, et al. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies[J]. J Natl Cancer Inst, 2002, 94(8): 606-616.
[4] PIKE M C, SPICER D V, DAHMOUSH L, et al. Estrogens,progestogens, normal breast cell proliferation, and breast cancer risk[J]. Epidemiol Rev, 1993, 15(1):17-35.
[5] KOSSMAN D A, WILLIAMS N I, DOMCHEK S M, et al. Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer[J]. J Appl Physiol, 2011, 111(6): 1687-1693.
[6] ANDRECHEK E R. HER2/Neu tumorigenesis and metastasis is regulated by E2F activator transcription factors[J]. Oncogene, 2015, 34(2): 217-225.
[7] PALMA G, FRASCI G, CHIRICO A, et al. Triple negative breast cancer looking for the missing link between biology and treatments[J]. Oncotarget, 2015, 6(29): 26560-26574.
[8] ZIEGLER R G, FUHRMAN B J, MOORE S C, et al. Epide-miologic studies of estrogen metabolism and breast cancer [J]. Steroids, 2015, 99(Pt A): 67-75.
[9] MASKARINEC G, BECKFORD F, MORIMOTO Y, et al. Association of estrogen measurements in serum and urine of premenopausal women[J]. Biomark Med, 2015, 9(5): 417-424.
[10] GREEN S, WALTER P, KUMAR V, et al. Human oestrogen receptor cDNA: sequence, expression and homology to verb-A[J]. Nature, 1986, 320(6058): 134-139.
[11] MADAK-ERDOGAN Z, GONG P, KATZENELLENBOGEN B S, et al. Differential utilization of nuclear and extranuclear receptor signaling pathways in the actions of estrogens, SERMs, and a tissue-selective estrogen complex (TSEC)[J]. J Steroid Biochem Mol Biol, 2016, 158: 198-206.
[12] COWLEY S M, HOARE S, MOSSELMAN S, et al. Estrogen receptors alpha and beta form heterodimers on DNA[J]. J Biol Chem, 1997, 272(32): 19858-19862.
[13] KIM J, SZINTE J S, BOULWARE M I, et al. 17β-estradiol and agonism of G-protein-coupled estrogen receptor enhance hippocampal memory via different cell-signaling mechanisms[J]. J Neurosci, 2016, 36(11): 3309-3321.
[14] ZHOU X, WANG S, WANG Z, et al. Estrogen regulates Hippo signaling via GPER in breast cancer[J]. J Clin Invest, 2015, 125(5): 2123-2135.
[15] ČÁSLAVSKÝ J, KLÍMOVÁ Z, VOMASTEK T, et al. ERK and RSK regulate distinct steps of a cellular program that induces transition from multicellular epithelium to single cell phenotype[J]. Cell Signal, 2013, 25(12): 2743-2751.
[16] SHI C, ZHU X, WANG J, et al. Estrogen receptor α promotes non-amyloidogenic processing of platelet amyloid precursor protein via the MAPK/ERK pathway[J]. J Steroid Biochem Mol Biol, 2014, 144(Pt B): 280-285.
[17] KIROUAC D C, DU J, LAHDENRANTA J, et al. HER2+ cancer cell dependence on PI3K vs. MAPK signaling axes is determined by expression of EGFR, ERBB3 and CDKN1B [J]. PLoS Comput Biol, 2016, 12(4): e1004827.
[18] ZHANG X, DENG H, WANG Z Y. Estrogen activation of the mitogen-activated protein kinase is mediated by ER-α36 in ER-positive breast cancer cells[J]. J Steroid Biochem Mol Biol, 2014, 143: 434-443.
[19] CRONAN M R, NAKAMURA K, JOHNSON NL, et al. Defining MAP3 kinases required for MDA-MB-231 cell tumor growth and metastasis[J]. Oncogene, 2012, 31(34): 3889-3900.
[20] MONTERO J C, OCAÑA A, ABAD M, et al. Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target[J]. PLoS One, 2009, 4(5): e5565.
|
|
|
|