Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours

Hall, Rosemary E.; Clements, Judith A.; Birrell, Stephen N.; Tilley, Wayne D.

doi:10.1038/bjc.1998.499

Cited by 48 publications

(36 citation statements)

References 33 publications

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“…This is consistent with our finding of higher levels in postmenopausal women without breast cancer, most of whom have very low levels of circulating estradiol, and with the fact that oral estrogen treatment lowers AAG levels in the blood (30). Positive immunoreactivity for GCDFP-15 in breast tumors was found to be highly dependent on androgen receptor status, but unrelated to estrogen or progesterone receptor (31). The identification of biomarkers of breast cancer in premenopausal women is of great importance because, compared with cancers in postmenopausal women, breast cancers that develop in these women are more likely to have a genetic cause, are less likely to respond to hormonal therapy, and are more likely to be aggressive (32).…”

Section: Discussionsupporting

confidence: 92%

Proteomic Analysis to Identify Breast Cancer Biomarkers in Nipple Aspirate Fluid

Alexander¹,

Stegner²,

Wagner‐Mann

et al. 2004

Clinical Cancer Research

154

100

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Purpose: Proteomic analysis of breast nipple aspirate fluid (NAF) holds promise as a noninvasive method to identify markers of breast cancer. The objectives of the study were to: (a) describe the NAF proteome, (b) identify candidate markers of breast cancer in NAF by using proteomic analysis, and (c) validate the markers identified by using a quantitative, high-throughput ELISA analysis.Experimental Design: For proteome analysis, NAF proteins from a single subject without breast cancer were separated by two-dimensional PAGE and were subjected to matrix-assisted laser desorption ionization time-of-flight mass spectometry identification. A total of 41 different proteins were identified, 25 of which were known to be secreted. To identify breast cancer markers, we separated 20 NAF samples (10 normal, 10 cancer) by two-dimensional PAGE. Three protein spots were detected that were up-regulated in three or more cancer samples. These spots were identified to be gross cystic disease fluid protein (GCDFP)-15, apolipoprotein D (apoD), and ␣1-acid glycoprotein (AAG). To validate these three potential biomarkers, 105 samples (53 from benign breasts and 52 from breasts with cancer) were analyzed using ELISA.Results: Among all of the subjects, GCDFP-15 levels were lower (P < 0.001) and AAG levels were higher (P ‫؍‬ 0.001) in breasts with cancer. This was also true in premenopausal (GCDFP-15, P ‫؍‬ 0.011; AAG, P ‫؍‬ 0.002) but not in postmenopausal women. GCDFP-15 levels were lowest (P ‫؍‬ 0.003) and AAG levels highest (P < 0.001) in women with ductal carcinoma in situ (DCIS). Menopausal status influenced GCDFP-15 and AAG more in women without breast cancer than in women with breast cancer. apoD levels did not correlate significantly with breast cancer.Conclusions: Our study revealed that the NAF proteome, as defined by two-dimensional PAGE, consists of a limited number of proteins, and that the expression of AAG and GCDFP-15 correlates with disease presence and stage.

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Section: Discussionsupporting

confidence: 92%

Proteomic Analysis to Identify Breast Cancer Biomarkers in Nipple Aspirate Fluid

Alexander¹,

Stegner²,

Wagner‐Mann

et al. 2004

Clinical Cancer Research

154

100

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“…Androgen receptor (AR) has been detected in almost 90% of breast cancer specimens (Bryan et al, 1984;Soreide et al, 1992) and has been shown to be a favourable prognostic factor for disease-free survival (KuenenBoumeester et al, 1996). The AR status and levels in breast cancer cells are positively correlated with the expression of a number of proteins, namely prostate-specific antigen (PSA) (Hall et al, 1998) and pepsinogen C (Balbin and Lopez. Otin, 1996) which are both up-regulated by androgens and act as markers of cell differentiation and favourable prognosis (Vozoso et al, 1995;Hahnel and Hahnel 1996;Scorilas et al, 1999).…”

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confidence: 99%

Codon 89 polymorphism in the human 5 α -reductase gene in primary breast cancer

et al. 2001

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SummaryThe enzyme human steroid 5-α reductase type II (SRD5A2) and androgen receptor (AR) are critical mediators of androgen action, suggesting a potential role in hormonally related cancers. The SRD5A2 gene harbours two frequent polymorphic sites, one in the coding region, at codon 89 of exon 1, where valine is substituted by leucine (V89L) and the other in the 3′ untranslated region (3′ UTR) where a variable number of dinucleotide TA repeat lengths exists. The V89L polymorphism is known to alter the activity of this enzyme. In the present study we examined 144 sporadic breast tumours from Italian patients for the V89L and TA polymorphisms by sequence and fragment analysis, respectively. Tumour extract prostate specific antigen (PSA) concentration as well as a number of well-established clinical and pathological parameters were evaluated. The results show that 53% of the tumours were homozygous for VV alleles, 37% were heterozygous for VL alleles and 10% were homozygous for LL alleles. TA(0) repeats were found in tumours with VV, LL and VL genotypes. TA(9) repeats were only found in VV homozygotes and were totally absent from either LL homozygotes or VL heterozygotes. PSA expression was significantly elevated in tumours with VV genotype. The presence of LL alleles in breast tumours is associated with earlier onset and shorter disease-free (RR = 2.65; P = 0.013) and overall survival (RR = 3.06; P = 0.014) rates. The VV genotype is associated with a more favourable prognosis. Our study suggests that the polymorphism in codon 89 of exon 1 of the human 5α-reductase gene is related with TA repeat genotypes, PSA expression and breast cancer prognosis. More specifically, we found that the LL genotype is also associated with earlier onset and more aggressive forms of breast cancer. Long-term-outcome studies are needed to investigate the relevance of this polymorphism to breast cancer susceptibility. substitution (A49T) along with the variable length dinucleotide TA repeats on the 3′ untranslated region of this gene occur sufficiently frequently in the population to be considered as gene polymorphisms (Vilchis et al, 1997). These alterations are capable of affecting the incidence of prostate cancer (Reichardt et al, 1995). These 2 single nucleotide changes as well as other mutations, as shown by site-directed mutagenesis, impair the reductase activity in one way or the other (Wigley et al, 1994;Makridakis et al, 1997;Makridakis et al, 2000). Decrease in the activity of this enzyme in prostate cancer has been linked to favourable prognosis (Kantoff et al, 1997). The decrease in prostate volume and PSA level in men treated with the reductase inhibitor finasteride, lends more credence to this idea (Gormley et al, 1992;Magklara et al, 1999Magklara et al, , 2000. No data is available on the role of this enzyme in breast cancer. In prostate cancer, the homozygote VV genotype of the V89L polymorphism has been associated with high reductase activity and high DHT levels. The homozygote LL genotype has been associated with low re...

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“…Another way to assess the activeness of the hormone receptor positive cells could be to exam the expression of their downstream proteins. Studies at different levels indicated that PSA and GCDFP are the AR downstream proteins and are co-expressed with AR in breast carcinomas [43][44][45][46] . However, using immunohistochemical staining on consecutive sections, we observed no immunohistochemically identifiable PSA expression in AR-positive luminal cells and no association between GCDFP and AR expression in luminal cells [34] .…”

Section: Reviewmentioning

confidence: 99%

Androgen Receptor (AR) and Breast Cancer: Reference to the AR Status in Normal/Benign Breast Luminal Cells

Wang

2015

Receptor Clin Invest

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Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours

Cited by 48 publications

References 33 publications

Proteomic Analysis to Identify Breast Cancer Biomarkers in Nipple Aspirate Fluid

Proteomic Analysis to Identify Breast Cancer Biomarkers in Nipple Aspirate Fluid

Codon 89 polymorphism in the human 5 α -reductase gene in primary breast cancer

Androgen Receptor (AR) and Breast Cancer: Reference to the AR Status in Normal/Benign Breast Luminal Cells

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