The aim of this research is to investigate the significance of clusterin (CLU) expression as a risk factor for breast cancer through tissue microarray technology and univariate analysis of overall survival. Formalin-fixed, paraffin-embedded tissues from 158 cases of breast cancer and 31 cases of normal adjacent tissues assembled into a tissue microarray. Cytoplasmic CLU expression in tumor tissues was measured by immunochemistry. Survival analysis was used to investigate the relationship between CLU expression and prognosis, tumor volume, pathological classification, and recurrence. Survival time of patients with CLU expression, lymph node metastasis, and limited post-surgery chemotherapy (<6 cycles of treatment) was significantly shorter than that of patients with no detectable CLU expression (P=0.000), without lymph node metastasis (P=0.000) and more comprehensive post-surgery chemotherapy (≥6 cycles of treatment) (P=0.035). CLU expression in tumor cells was higher than in normal adjacent breast epithelial cells (P=0.03). The CLU expression staining coefficient of cancer tissues with lymph node metastasis was higher than those without lymph node metastasis (P=0.000). Cytoplasmic CLU expression was found to be a prognostic factor for human breast cancer.
KurbetS., de BarrosA. C., PinottiJ. A.The Safe Association of Intraoperative Evaluation of Surgical Margins and Neoadjuvant Chemotherapy in Breast Cancer Larger than 3 Centimeters. Tumori92, 21–25 (2006).
2.
WapnirI. L., AndersonS. J., MamounasE. P., GeyerC. E.Jr., JeongJ. H., Tan-ChiuE, FisherB., WolmarkN.Prognosis after Ipsilateral Breast Ttumor Recurrence and Locoregional Recurrences in Five National Surgical Adjuvant Breast and Bowel Project Node-positive Adjuvant Breast Cancer Trials. J Clin Oncol24, 2028–2037 (2006).
3.
PajakB., OrzechowskiA.Clusterin: The Missing Link in the Calcium-dependent Resistance of Cancer Cells to Apoptogenic Stimuli. Postepy Hig Med Dosw (Online)60, 45–51 (2006).
4.
NickersonT., PollakM., HuynhH.Castration-induced Apoptosis in the Rat Ventral Prostate is Associated with Increased Expression of Genes Encoding Insulin-like Growth Factor Binding Proteins 2, 3, 4, and 5. Endocrinology139, 807–810 (1998).
5.
YangC. R., LeskovK., Hosley-EberleinK., CriswellT., PinkJ. J., KinsellaT. J., BoothmanD. A.Nuclear Clusterin/XIP8, An X-ray-induced Ku70-binding Protein that Signals Cell Death. Proc Natl Acad Sci USA97, 5907–5912 (2000).
6.
VanWeeldenK., FlanaganL., BinderupL., TenniswoodM., WelshJ.Apoptotic Regression of MCF-7 Xenografts in Nude Mice Treated with the Vitamin D3 Analog, EB1089. Endocrinology139, 2102–2110 (1998).
7.
PucciS., BonannoE., PichiorriF., AngeloniC., SpagnoliL. G.Modulation of Different Clusterin Isoforms in Human Colon Tumorigenesis. Oncogene23, 2298–2304 (2004).
RedondoM., VillarE., Torres-MunozJ., TellezT., MorellM., PetitoC. K.Overexpression of Clusterin in Human Breast Carcinoma. Am J Pathol157, 393–399 (2000).
10.
GoldbergG. S., JinZ., IchikawaH., NaitoA., OhkiM., El-DeiryW. S., TsudaH.Global Effects of Anchorage on Gene Expression During Mammary Carcinoma Cell Growth Reveal Role of Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Anoikis. Cancer Res61, 1334–1337 (2001).
11.
SchedinP., MitrengaT., KaeckM.Estrous Cycle Regulation of Mammary Epithelial Cell Proliferation, Differentiation, and Death in the Sprague-Dawley Rat: A Model for Investigating the Role of Estrous Cycling in Mammary Carcinogenesis. J Mammary Gland Biol Neoplasia5, 211–225 (2000).
12.
BiroccioA., D'AngeloC., JansenB., GleaveM. E., ZupiG.Antisense Clusterin Oligodeoxynucleotides Increase the Response of HER-2 Gene Amplified Breast Cancer Cells to Trastuzumab. J Cell Physiol204, 463–469 (2005).
13.
SoA., SinnemannS., HuntsmanD., FazliL., GleaveM.Knockdown of the Cytoprotective Chaperone, Clusterin, Chemosensitizes Human Breast Cancer Cells both In Vitro and In Vivo. Mol Cancer Ther4, 1837–1849 (2005).
14.
FanJ., WangL., WangX. J., WuJ., LuJ. S., DiG. H., ShenK. W., HanQ. X., LiuB. L., ShenZ. Z., ShaoZ. M.Breast Conservative Therapy in East Part of China: A Retrospective Cohort Study. J Cancer Res Clin Oncol132, 573–578 (2006).
15.
CuiY., ShuX. O., GaoY. T., CaiH., TaoM. H., ZhengW.Association of Ginseng Use with Survival and Quality of Life Among Breast Cancer Patients. Am. J. Epidemiol.163, 645–653 (2006).
16.
FangY., ShiL. Y.Comprehensive Evaluation and Trend Prediction of Risk Factors on Breast Cancer. Zhonghua Liu Xing Bing Xue Za Zhi24, 611–614 (2003).
17.
NabH. W., CoeberghJ. W.Support and Treatment of Serious Comorbidity Also Improve Survival in Breast Cancer. BMJ315, 191 (1997).
18.
CristofanilliM.Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer. Semin Oncol33, S9–14 (2006).
19.
WoodwardW. A., Vinh-HungV., UenoN. T., ChengY. C., RoyceM., TaiP., VlastosG., WallaceA. M., HortobagyiG. N., NietoY.Prognostic Value of Nodal Ratios in Node-positive Breast Cancer. J Clin Oncol24, 2910–2916 (2006).
20.
DixonJ. M.Extended Adjuvant Therapy with Letrozole: Reducing the Risk of Recurrence. Expert Rev Anticancer Ther6, 849–859 (2006).
21.
TairaN., AogiK., OhsumiS., TakashimaS., NishimuraR., DoiharaH., SaekiT.S-1 (TS-1) Maintained Complete Response for Approximately 10 Years in a Case of Metastatic Breast Cancer. Breast Cancer13, 220–224 (2006).
22.
XieZ., Harris-WhiteM. E., WalsP. A., FrautschyS. A., FinchC. E., MorganT. E.Apolipoprotein J (Clusterin) Activates Rodent Microglia In Vivo and In Vitro. J Neurochem93, 1038–1046 (2005).
23.
ZanjaniH., FinchC. E., KemperC., AtkinsonJ., McKeelD., MorrisJ. C., PriceJ. L.Complement Activation in Very Early Alzheimer Disease. Alzheimer Dis Assoc Disord19, 55–66 (2005).
24.
MalloryJ. C., CruddenG., OlivaA., SaundersC., StrombergA., CravenR. J.A Novel Group of Genes Regulates Susceptibility to Antineoplastic Drugs in Highly Tumorigenic Breast Cancer Cells. Mol Pharmacol68, 1747–1756 (2005).
25.
GuthS. E., BohmS., MusslerB. H., EisenbrandG.Sensitive In Vitro Test Systems to Determine Androgenic/Antiandrogenic Activity. Mol Nutr Food Res48, 282–291 (2004).
26.
Simboli-CampbellM., NarvaezC. J., van WeeldenK., TenniswoodM., WelshJ.Comparative Effects of 1, 25(OH)2D3 and EB1089 on Cell Cycle Kinetics and Apoptosis in MCF-7 Breast Cancer Cells. Breast Cancer Res Treat42, 31–41 (1997).
27.
CaccamoA. E., ScaltritiM., CaporaliA., D'ArcaD., ScorcioniF., CandianoG., MangiolaM., BettuzziS.Nuclear Translocation of a Clusterin Isoform is Associated with Induction of Anoikis in SV40-immortalized Human Prostate Epithelial Cells. Ann N Y Acad Sci1010, 514–519 (2003).
28.
BurkeyB. F., deSilvaH. V., HarmonyJ. A.Intracellular Processing of Apolipoprotein J Precursor to the Mature Heterodimer. J Lipid Res32, 1039–1048 (1991).
29.
DoustjalaliS. R., YusofR., YipC. H., LooiL. M., PillayB., HashimO. H.Aberrant Expression of Acute-phase Reactant Proteins in Sera and Breast Lesions of Patients with Malignant and Benign Breast Tumors. Electrophoresis25, 2392–2401 (2004).
30.
ChenH., TrittonT. R., KennyN., AbsherM., ChiuJ. F.Tamoxifen Induces TGF-beta 1 Activity and Apoptosis of Human MCF-7 Breast Cancer Cells In Vitro. J Cell Biochem61, 9–17 (1996).
31.
JamesS. Y., MackayA. G., ColstonK. W.Effects of 1, 25 Dihydroxyvitamin D3 and its Analogues on Induction of Apoptosis in Breast Cancer Cells. J Steroid Biochem Mol Biol58, 395–401 (1996).
32.
WarriA. M., HuovinenR. L., LaineA. M., MartikainenP. M., HarkonenP. L.Apoptosis in Toremifene-induced Growth Inhibition of Human Breast Cancer Cells In Vivo and In Vitro. J Natl Cancer Inst85, 1412–1418 (1993).
33.
CriswellT., KlokovD., BemanM., LavikJ. P., BoothmanD. A.Repression of IR-inducible Clusterin Expression by the p53 Tumor Suppressor Protein. Cancer Biol Ther2, 372–380 (2003).
34.
WelshJ.Induction of Apoptosis in Breast Cancer Cells in Response to Vitamin D and Antiestrogens. Biochem Cell Biol72, 537–545 (1994).
35.
NarvaezC. J., VanweeldenK., ByrneI., WelshJ.Characterization of a Vitamin D3-resistant MCF-7 Cell Line. Endocrinology137, 400–409 (1996).
36.
RennieP. S., MawjiN. R., ColdmanA. J., GodolphinW., JonesE. C., VielkindJ. R., BruchovskyN.Relationship Between Variant Forms of Estrogen Receptor RNA and an Apoptosis-related RNA, TRPM-2, With Survival in Patients with Breast Cancer. Cancer72, 3648–3654 (1993).
37.
Simboli-CampbellM., NarvaezC. J., TenniswoodM., WelshJ.1, 25-Dihydroxyvitamin D3 Induces Morphological and Biochemical Markers of Apoptosis in MCF-7 Breast Cancer Cells. J Steroid Biochem Mol Biol58, 367–376 (1996).
38.
HuovinenR., WarriA., CollanY.Mitotic Activity, Apoptosis and TRPM-2 mRNA Expression in DMBA-induced Rat Mammary Carcinoma Treated with Anti-estrogen Toremifene. Int J Cancer55, 685–691 (1993).
