Cancer Cell International | |
Expression pattern of the apoptosis-stimulating protein of p53 family in p53+ human breast cancer cell lines | |
Xuexia Lv1  Ping Wang1  Jian Yin1  Yanping Chen1  Chunfang Gao1  Changsong Wang1  | |
[1] Department of Pathology, 150th Hospital of PLA, Luoyang, Henan Province, China | |
关键词: p53; Apoptosis; Breast cancer cell line; ASPP family member; | |
Others : 792583 DOI : 10.1186/1475-2867-13-116 |
|
received in 2013-08-07, accepted in 2013-11-13, 发布年份 2013 | |
【 摘 要 】
Background
The apoptosis-stimulating protein of p53 (ASPP) family comprises three members, namely, ASPP1, ASPP2, and iASPP. They regulate the promotive effect of p53 on apoptosis. Breast cancer (BC) remains as one of the leading causes of cancer or cancer-related mortality among women. However, the relationship between the ASPP family members and p53, as well as the dissemination and expression pattern of ASPP family members in p53+ BC, has not been elucidated. Our objectives are to detect the expression of ASPP family members in p53+ BC cell lines and determine its significance in tumor cell apoptosis.
Methods
The mRNA expression of ASPP family members in five p53+ BC cell lines was detected through RT-PCR and assayed using Quality-one software. The p53 protein expression was detected by immunohistochemistry. Afterward, the apoptosis indices of the five BC cell lines were detected by flow cytometry.
Results
The iASPP mRNA was expressed in Bcap-37, MCF-7, and HBL-100. Compared with the human peripheral blood mononuclear cells, significant differences were found in the ASPP1 mRNA in Bcap-37, MDA-MB-231, MCF-7, and HBL-100 (p < 0.05), except that in ZR-75-30 (p > 0.05). The ASPP2 mRNA was expressed in MDA-MB-231, Bcap-37, and MCF-7, but not in HBL-100 and ZR-75-30. The p53 protein was expressed in five breast cancer cell lines. ZR-75-30 and MDA-MB-231 apoptosis indices were higher than those of other breast cancer cell line and peripheral blood mononuclear cells (p < 0.01).
Conclusions
The mRNA expression of ASPP family members varied in the five p53+ BC cell lines. The results also verified that the family members have an important function in apoptosis, which was promoted by p53 protein. ZR-75-30 BC showed high apoptosis index, without expression of any ASPP family members, indicating that the pathway of apoptosis in this cell line may be related to other cell transduction pathway. MDA-MB-231, Bcap37, and MCF-7 cell lines all expressed ASPP1/2. However, the apoptosis pathway in MDA-MB-231 is different from those of the other two cell lines. The status of the different cell lines should also be considered when the functions of the ASPP family members are examined.
【 授权许可】
2013 Wang et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140705032955234.pdf | 796KB | download | |
Figure 3. | 29KB | Image | download |
Figure 2. | 143KB | Image | download |
Figure 1. | 77KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Parkin DM, Bray F, Ferlay J, Pisani P: Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001, 94:153-156.
- [2]Bhatia P, Sanders MM, Hansen MF: Expression of receptor activator of nuclear factorkappaB is inversely correlated with metastatic phenotype in breast carcinoma. Clin Cancer Res 2005, 11:162-165.
- [3]Kakarala M, Wicha MS: Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 2008, 26:2813-2820.
- [4]Patel SA, Heinrich AC, Reddy BY, Srinivas B, Heidaran N, Rameshwar P: Breast cancer biology: the multifaceted roles of mesenchymal stem cells. J Oncol 2008, 2008:425895.
- [5]Ferlay J, Shin HR, Bray F, et al.: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127:2893-2917.
- [6]Samuels-Lev Y, O’Connor DJ, Bergamaschi D, et al.: ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell 2001, 8:781-794.
- [7]Lane D: How cells choose to die? Nature 2001, 414:25-27.
- [8]Brooksbank C: APOPTOSIS: ASPP bites. Nat Rev Cancer 2001, 1:92.
- [9]Gresham D: Apoptosis: cheating death. Nat Rev Mol Cell Biol 2003, 4:87.
- [10]Slee EA, Gillotin S, Bergamaschi D, et al.: The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization. Oncogene 2004, 23:9007-9016.
- [11]Liu ZJ, Lu X, Zhang Y, et al.: Downregulated mRNA expression of ASPP and the hypermethylation of the 5′-untranslated region in cancer cell lines retaining wild-type p53. FEBS Lett 2005, 579:1587-1590.
- [12]Bergamaschi D, Samuels Y, Jin B, et al.: ASPP1 and ASPP2: common activators of p53 family members. Mol Cell Biol 2004, 24:1341-1350.
- [13]Bergamaschi D, Samuels Y, O’Neil NJ, et al.: iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat Genet 2003, 33:162-167.
- [14]Liu Z-J, Cai Y, Hou L, et al.: Effect of RNA interference of iASPP on the apoptosis in MCF-7 breast cancer cells. Cancer Invest 2008, 26(9):878-9882.
- [15]Vives V, Su J, Zhong S, et al.: ASPP2 is a haploinsufficient tumor suppressor that cooperates with p53 to suppress tumor growth. Genes Dev 2006, 20:1262-1267.
- [16]Lettre G, Kritikou EA, Jaeggi M, et al.: Genome-wide RNAi identifies p53-dependent and -independent regulators of germ cell apoptosis in C. elegans. Cell Death Differ 2004, 11:1198-1203.
- [17]Nexo BA, Vogel U, Olsen A, et al.: Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP. BMC Med Genet 2008, 9:56.
- [18]Wang Y, Godin-Heymann N, Wang XD, et al.: ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells. Cell Death Differ 2013, 20:525-534.
- [19]Arnaud MV, Robert LL, Karen HV: Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP. Genes Dev 2010, 24:2430-2439.
- [20]Robinson RA, Lu X, Jones EY, Siebold C: Biochemical and structural studies of ASPP proteins reveal differential binding to p53, p63, and p73. Structure 2008, 16:259-268.
- [21]Jayendra BP, Kinjal DP, Shruti RP, et al.: Recent candidate molecular markers: vitamin D signaling and apoptosis specific regulator of p53 (ASPP) in breast cancer. Asian Pacific J Cancer Prev 2012, 13:1727-1735.
- [22]Anissa C, Rubeta NHM, Valentina S, et al.: iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia. EMBO J 2011, 30:4261-4273.