Antiangiogenic Activity of Prostate-Specific Antigen

Fortier, Anne H.; Nelson, Barbara J.; Grella, Davida K.; Holaday, John W.

doi:10.1093/jnci/91.19.1635

Cited by 183 publications

(112 citation statements)

References 18 publications

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“…Lai et al (1996) have reported that PSA stimulates the conversion of the potent estradiol (E2) to the less potent estrone (E1), thereby inhibiting the growth of certain breast cancer cell lines in vitro. Antiangiogentic and antimetasatic properties have also been demonstrated recently (Balbay et al 1999;Fortier et al 1999). PSA proteolytically cleaves parathyroid hormonerelated protein (PTHrP) (Iwamura et al 1996), which is present in both seminal fluid and breast tissue.…”

Section: Discussionmentioning

confidence: 94%

Novel polymorphisms of prostate-specific antigen (PSA) gene associated with PSA mRNA expression in breast cancer

et al. 2000

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A growing body of evidence suggests that prostate-specific antigen (PSA) is a novel prognostic factor for breast cancer. The molecular mechanism of variant PSA expression in breast cancer has remained poorly understood in spite of intensive research. Previous studies have shown that the coding region of the PSA gene is not a target for mutations in prostate cancer and breast cancer. The purpose of this study was to analyze genetic variations in the promoter region of the PSA gene, and to detect whether such variations are correlated with PSA mRNA expression in breast tumors. We identified two polymorphisms in the proximal promoter region of the PSA gene. These polymorphisms are located at positions Ϫ252 (G or A) and Ϫ205 (A or AA), and generate three genotypes. The genotypes were associated with PSA mRNA expression. Our findings suggest that these polymorphisms identified in the proximal promoter region may affect the transcriptional activity of PSA.

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Section: Discussionmentioning

confidence: 94%

Novel polymorphisms of prostate-specific antigen (PSA) gene associated with PSA mRNA expression in breast cancer

et al. 2000

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“…Some serine proteases belonging to the kallikrein family, such as PSA and normal epithelial cell-specific-1 (NES1) gene have been connected to prevention of malignant processes of cells. A recent report shows that PSA has antiangiogenic activity, 19 while NES1 is suggested to be a tumor suppressor. 20 Overexpression of the TMPRSS2 gene, as shown here, together with the fact that genomic rearrangements such as a loss of heterozygosity are uncommon at the locus of this gene, suggest that TMPRSS2 does not fulfill all the criteria of a potential tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

TheTMPRSS2 gene encoding transmembrane serine protease is overexpressed in a majority of prostate cancer patients: Detection of mutatedTMPRSS2 form in a case of aggressive disease

et al. 2001

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The serine protease TMPRSS2 gene expression was studied by in situ hybridization using benign prostatic hyperplasia and prostate cancer tissue samples from 32 patients. Expression of TMPRSS2 gene was higher in cancer cells than that in benign cells in 84% of the specimens containing both benign and malignant tissues. The TMPRSS2 mRNA level was significantly increased in poorly differentiated (p ‫؍‬ 0.014, n ‫؍‬ 7) and untreated (p ‫؍‬ 0.022, n ‫؍‬ 13) primary prostate adenocarcinomas compared to benign tissues. In addition, androgen-deprivation therapy significantly decreased the expression of TMPRSS2 in benign prostate tissue (p ‫؍‬ 0.07), which is in accordance with the androgen-inducible expression of the gene. The gene copy number of TMPRSS2, analyzed by competitively differential PCR, was duplicated in the malignant cells of about 38% of the prostate cancer patients analyzed. Thus, the increase in the gene copy number is probably not the primary reason for the detected overexpression of the TMPRSS2 gene. Mutations in the TMPRSS2 gene were screened using DNA isolated from paraffin-embedded prostate cancer tissues from 9 patients with aggressive prostate cancer and from 9 patients with nonaggressive disease. Thirteen exons covering the coding region were checked using enzymatic mutation detection and direct sequencing. One patient with aggressive prostate cancer carried a deletion and a stop codon in exon 11, leading to inactivation of the serine protease domain in TMPRSS2.

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“…Many authors have observed that PSA possesses anti-angiogenic properties and breast cancer cases having higher levels of PSA shows better prognosis [33]. Considering the heterogeneity of the population of breast cancer cases, additional evaluation of PSA in relation to stage of tumor, risk of relapse and metastasis is required to reach at a definitive conclusion regarding assessment of its utility as a diagnostic and prognostic marker in breast cancer.…”

Section: Rank Of Serum Tpsa Rank Of Serum Testosteronementioning

confidence: 99%