Up-regulation of human secreted frizzled homolog in apoptosis and its down-regulation in breast tumors

Zhou, Zhongjun; Wang, Jianming; Han, Xiaoliang; Zhou, Jia‐Guo; Linder, Stig

doi:10.1002/(sici)1097-0215(19980925)78:1<95::aid-ijc15>3.0.co;2-4

Cited by 88 publications

(65 citation statements)

References 21 publications

(19 reference statements)

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“…To examine sFRP-induced e ects on Wnt signaling in glioma cells in vitro, we stably expressed sFRP transgenes in human malignant glioma cell lines with (U373MG) or without (U87MG, LN-229) endogenous sFRP expression. Contrary to recent reports which have suggested an association of serum deprivation-induced G1 arrest and induction of sFRPs (Zhou et al, 1998), ectopic expression of sFRP-1 or sFRP-2 had no e ect on cell cycle distribution (data not shown). Thus, although sFRP expression depended on con¯uency which is associated with accumulation in G0/1 in glioma cells (Hueber et al, 1998), cell cycle regulation was una ected by ectopic expression of sFRP, suggesting that sFRP do not mediate the con¯uency-induced G0/1 arrest.…”

Section: Discussioncontrasting

confidence: 99%

“…It has been reported that serum starvation-induced G1 arrest of breast epithelial cells was associated with induction of sFRP-1, suggesting a role of sFRPs in the regulation of the cell cycle (Zhou et al, 1998). Therefore, we carried out cell cycle analysis by¯ow cytometry, but did not ®nd signi®cant di erences between the neo and sFRP-expressing cell lines under normal growth conditions.…”

Section: Malignant Glioma Cells Express Sfrpsmentioning

confidence: 92%

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Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

et al. 2000

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Cellular resistance to multiple proapoptotic stimuli and invasion of surrounding brain tissue by migrating tumor cells are main obstacles to an e ective therapy for human malignant glioma. Here, we report that the Wnt family of embryonic di erentiation genes modulate growth of malignant glioma cells in vitro and in vivo and inhibit cellular migration in vitro. sFRPs (soluble Frizzled-related proteins) are soluble proteins that bind to Wnt and interfere with Wnt signaling. We ®nd that sFRP-1 and sFRP-2 are produced by the majority of longterm and ex vivo malignant glioma cell lines. Glioma cells that ectopically express sFRPs exhibit increased clonogenicity and enhanced resistance to serum starvation. In contrast, sFRPs do not modulate glioma cell susceptibility to apoptosis induced by the cytotoxic cytokines, CD95 (Fas/APO-1) ligand (CD95L) or Apo2 ligand/tumor necrosis factor-related apoptosisinducing ligand (Apo2L/TRAIL), or various cytotoxic drugs. sFRP-2 strongly promotes the growth of intracranial glioma xenografts in nude mice. In contrast, enhanced expression of sFRPs inhibits the motility of glioma cells in vitro. sFRP-mediated e ects on glioma cells are accompanied by decreased expression and activity of matrix metalloproteinase-2 (MMP-2) and decreased tyrosine phosphorylation of b-catenin. Thus, sFRPs promote survival under non-supportive conditions and inhibit the migration of glioma cells. We suggest that the regulation of these cellular processes involves expression of MMP-2 and tyrosine phosphorylation of bcatenin. These data support a function for Wnt signaling and its modulation by sFRPs in the biology of human gliomas. Oncogene (2000) 19, 4210 ± 4220.

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Section: Discussioncontrasting

confidence: 99%

Section: Malignant Glioma Cells Express Sfrpsmentioning

confidence: 92%

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

et al. 2000

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“…SFRP1 was found to be regulated through the cellcycle mechanism and accumulated in growth-arrested or apoptotic cells (Melkonyan et al, 1997;Zhou et al, 1998). To investigate whether the modulation of SFRP1 expression is associated with di erences in apoptotic activity, TUNEL assays were done on 38 sections derived from samples for which the SFRP1 status was known (19 SFRP1-positive and 19 SFRP1-negative samples).…”

Section: Apoptosis Analysismentioning

confidence: 99%

“…Upregulation of SFRP1 has been associated with apoptosis (Melkonyan et al, 1997;Zhou et al, 1998), and downregulation has been found in breast tumors (Ugolini et al, 1999;Zhou et al, 1998). SFRPs ectopic expression promotes growth and inhibits motility of malignant glioma cells (Roth et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

WNT pathway and mammary carcinogenesis: Loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type

Ugolini¹,

et al. 2001

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Secreted Frizzled-related protein 1 (SFRP1) encodes a member of a protein family that contains a cysteine-rich domain similar to the WNT-binding site of Frizzled receptors and regulates the WNT pathway. The WNT pathway is frequently altered in human cancers. We have de®ned the pattern of SFRP1 mRNA expression in the progression of breast cancer. We show that SFRP1 is expressed in the epithelial component of normal breast, in the in situ component of ductal carcinomas and is lost in more than 80% of invasive breast carcinomas except the medullary type. Loss of SFRP1 expression is correlated with the presence of hormonal receptors. Conversely, the maintenance of SFRP1 in carcinomas is correlated with the presence of lymphoplasmocytic stroma. No signi®cant association was observed between SFRP1 status and the level of apoptosis in tumoral cells. Oncogene (2001) 20, 5810 ± 5817.

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“…sFRP1 directly binds to Wnt proteins and can actively regulate Wnt activity. 37 Upregulation of sFRP1 has been associated with apoptosis, 38,39 and downregulation has been found in more than 80% of invasive breast tumors. 40 Recently, epigenetic inactivation by promoter hypermethylation of several sFRP proteins, including sFRP1, could be demonstrated in colorectal and gastric cancers.…”

mentioning

confidence: 99%

Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer

Stoehr

Wissmann²,

Suzuki³

et al. 2004

Laboratory Investigation

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101

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Many molecular alterations are known to occur in urothelial carcinoma of the bladder, but their significance for tumor progression is poorly understood. Deletions of chromosome 8p are frequently found in several tumor types and are often associated with progressive disease. In all, 99 bladder tumors were screened for deletions at 8p using loss of heterozygosity (LOH) and multicolor fluorescence in situ hybridization FISH analyses. Allelic loss on chromosome 8p in at least one marker was found in 25/99 (25%) tumors. There was a significant correlation of 8p deletions with invasive tumor growth and a highly significant association with papillary growth pattern in patients with invasive disease. cDNA array analyses revealed that secreted Frizzled-related protein 1 (sFRP1), an antagonist of Frizzled receptors and Wnt pathway activation on chromosome 8p12-11.1, is frequently downregulated in bladder cancer. To investigate sFRP1 as a candidate for a putative progressionrelated gene on 8p, urothelial cell lines and primary urothelial carcinomas were screened for sFRP1 expression using quantitative real-time PCR, Northern blot, immunofluorescence and immunohistochemistry (IHC). Of the investigated bladder cancers, 38% showed loss of sFRP1 expression by quantitative RT-PCR. Evaluation of the protein expression by IHC using tissue microarrays containing 776 bladder cancers revealed loss or strong reduction of sFRP1 expression in 66% of cases. SFRP1 loss was associated with higher tumor stage and grade and shorter overall survival. In addition, loss of sFRP1 was an independent indicator of poor survival in patients with papillary but not with muscle invasive bladder cancer. There were neither mutations in the coding region of sFRP1 nor homozygous deletions at 8p12-11.21. However, promoter methylation was detected using methylation-specific PCR in 29% of cases. In conclusion, we could show a close correlation of chromosome 8p deletions and progression of papillary bladder tumors. The sFRP1 gene on chromosome 8p12-11.1 could be a candidate gene for the predicted, progression-related tumor suppressor gene in bladder cancer and could contribute to urothelial carcinogenesis.

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Up-regulation of human secreted frizzled homolog in apoptosis and its down-regulation in breast tumors

Cited by 88 publications

References 21 publications

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

WNT pathway and mammary carcinogenesis: Loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type

Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer

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