High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity

Adamson, Janet; Morgan, Elwin A; Beesley, Carol; Mei, Yongqiang; Foster, Christopher S.; Fujii, Hiroshi; Rudland, Philip S.; Smith, Paul; Ke, Youqiang

doi:10.1038/sj.onc.1206341

Cited by 109 publications

(100 citation statements)

References 34 publications

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“…Previous invasion assays have demonstrated the benign nature of PNT-2 cells and the progressively malignant characteristics of LNCaP, Du-145 and PC-3, in terms of their ability invade basement membranes in vitro. 30,31 Western blot also detected nearly a 6-fold of increment of OPN expression in the highly malignant tissues when compared with those expressed in the normal and BPH samples (Fig. 2).…”

Section: Discussionmentioning

confidence: 93%

Prognostic significance of osteopontin expression in human prostate cancer

Forootan

Foster

Aachi

et al. 2005

Intl Journal of Cancer

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To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of prostate cancer, the status of OPN expression in benign and malignant prostate cancer cell lines and tissues was analysed by Western blot and immunohistochemistry. Amongst the four prostate cell lines analysed, the level of OPN expressed in the benign PNT-2 cells was set at 1, the relative level of OPN expressed in the weakly malignant cell line LNCaP was increased to 1.5. In the highly malignant cell lines Du-145 and PC-3, the level of OPN expression was further increased to 2.9 and 4.4, respectively. An increased expression of OPN was also observed in the prostate tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign prostate hyperplasia (BPH) was similar at 0.99 6 0.2, whereas the OPN level in the highly malignant carcinoma tissue was greatly increased by nearly 6-fold to 5.9 6 0.3. Amongst the 116 cases examined immunocytochemically, of the 10 normal cases, 3 (30%) were unstained and 7 (70%) stained weakly positive (1). Amongst the 36 BPH samples, 32 (89%) stained weakly positive (1) and 4 (11%) were unstained (2). For the 70 carcinomas analysed, 31 (44%) stained strongly positive (111), 20 (29%) stained moderately positive (11) and 19 (27%) stained weakly positive (1). These results showed that the level of OPN expressed between the normal and the BPH samples was not significantly different (Fisher's exact test, p 5 0.16). However, in comparison to that in the BPH samples, the expression of OPN in the carcinoma tissues was significantly increased (Chi-square test, p < 0.0001). Kaplan-Meier survival analysis showed that the increased level of OPN expression was significantly (n 5 70, p 5 0.03) associated with reduced survival time of the patients. The OPN expression was increased with the increasing Gleason scores of the carcinomas (Chi-square test, p < 0.001). The results in our study support our hypothesis and suggest that the increased OPN level may be involved in the malignant transformation of prostate epithelial cells and OPN expression level is an important determinant for patient survival. ' 2005 Wiley-Liss, Inc.Key words: prostate carcinoma; osteopontin; benign prostate hyperplasia (BPH); Gleason scores; patient survival Prostate cancer has become the most common male cancer and the second leading cause of death from male malignant disease in the United States and Europe, and this disease kills more than 40,000 men per year in the developed world. 1,2 Despite the increasing incidence, the molecular basis of prostate cancer progression, invasion and metastasis is still not fully understood. The complicated molecular pathology of prostate cancer may involve a series of sequential genetic events, which cause the initiation and progression of the malignant changes of prostate epithelial cells. The complicated genetic events responsible for tumorigenicity and metastasis of prostate cancer may be classified in a simple ...

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Section: Discussionmentioning

confidence: 93%

Prognostic significance of osteopontin expression in human prostate cancer

Forootan

Foster

Aachi

et al. 2005

Intl Journal of Cancer

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“…Up-regulation of FABP5 RNA and protein has been observed in prostate and breast cancer cell lines relative to benign cell lines. 34,35 Furthermore, overexpression of FABP5 in a rat mammary epithelial cell line induces metastasis. 35,36 Most notably, recent studies by Noy and colleagues 11,12 have demonstrated a role for FABP5 in mediating RA action in a mouse mammary cancer model and human breast cancer cell lines by targeting PPAR␤, a nuclear receptor associated with cell survival/proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…34,36,47 Furthermore, depletion of FABP5 in a prostate cancer cell line dramatically inhibited cell proliferation and tumorigenicity in nude mice. 48 Another member of the FABP family, FABP4, which is closely related to FABP5, has recently been shown to be associated with increased breast cancer risk in obese patients.…”

Section: Discussionmentioning

confidence: 99%

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

Liu

Graham

Glubrecht

et al. 2011

The American Journal of Pathology

140

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Recent studies using animal models suggest that expression of FABP5 drives the stimulation of cell growth observed in estrogen receptor (ER)-negative breast cancer cells on exposure to retinoic acid (RA). The purpose of this study was to investigate the clinicopathological significance of FABP5 in breast cancer and to evaluate FABP5 as a prognostic marker and a possible novel therapeutic target in breast cancer. Gene expression microarray analysis revealed a significant correlation between elevated FABP5 RNA levels and ER/ progesterone receptor (PR)-negative status, high tumor grade, and poor prognosis. Tissue microarray analysis demonstrated similar correlations with cytoplasmic FABP5 protein. Based on multivariate proportional regression analysis, cytoplasmic FABP5 is a significant and independent prognostic marker of overall survival and recurrence-free survival in breast cancer. The effects of FABP5 on tumor growth appear to be mediated primarily through cytoplasmic FABP, because no correlation was found between nuclear FABP5 and ER/PRnegative status, recurrence, and survival. FABP5 knockdown in breast cancer cell lines demonstrates a correlation between FABP5 levels and growth response to RA. We propose a model whereby growth-promoting FABP5 competes with growth-inhibiting CRABP2 for RA, with retention of RA in the cytoplasm by FABP5 preventing the inhibition of tumor growth. (Am J Pathol

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“…26 It is suggested to be a metastasis-inducing gene in prostate cancer through vegf (vascular endothelial growth factor) gene up-regulation. 27,28 With regard to A-FABP, the protein on which we have focused our attention, its expression is also down-regulated in breast cancer cell lines in comparison with breast normal cell lines. 29 Meantime, there have been few studies on FABP family members' expression in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

Boiteux

Lascombe

Roche

et al. 2009

Intl Journal of Cancer

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Superficial pT1 bladder tumors are characterized by a high risk of recurrence and progression in grade and stage. Few studies provided evidence that loss of adipocyte-fatty acid binding protein (A-FABP) expression was associated with bladder cancer progression. A-FABP is a lipid binding protein playing a role in intracellular lipid transport and metabolism, as well as in signal transduction. We reported from bladder tumors that decrease of A-FABP transcript level significantly correlated to tumor stage and to histologic grade (p < 0.05). Namely, in poor prognosis high grade pT1 tumors there was a loss of A-FABP expression compared to good prognosis tumors suggesting that re-expression of A-FABP could be a therapeutic approach in early stage bladder cancer to prevent disease progression. We demonstrated for the first time that this marker is upregulated by Peroxisome Proliferator-Activated Receptor (PPAR) a, b and c in T24 cells (derived from an undifferentiated grade III carcinoma) and only by PPARb in RT4 cells (derived from a well differentiated grade I papillary tumor). This effect occurred through a PPAR-dependent transcriptional mechanism without modifying mRNA stability and interestingly required de novo protein synthesis. Data as a whole suggest a prognostic significance of A-FABP in bladder cancer outcome and the potential utility of overexpression of this protein by PPAR agonists open up new perspectives in the treatment of bladder cancer.

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High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity

Cited by 109 publications

References 34 publications

Prognostic significance of osteopontin expression in human prostate cancer

Prognostic significance of osteopontin expression in human prostate cancer

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

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