Anti-CYP4Z1 autoantibodies detected in breast cancer patients

Nunna, Venkatrao; Jalal, Nasir; Bureik, Matthias

doi:10.1038/cmi.2017.21

Cited by 31 publications

(17 citation statements)

References 9 publications

(10 reference statements)

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“…Our results are concordant with previous studies demonstrating high CYP4Z1 expression in tumours of the breast, ovary and prostate compared to normal tissues [4][5][6][7][8]11,28 . Additionally, a strong over-expression of CYP4Z1 was seen in metastatic tumour samples compared with primary tumours 6,8 .…”

Section: Discussionsupporting

confidence: 93%

“…The current study investigated the CYP4Z1 and CYP1B1 expressions across a panel of different types of bladder cancer to con rm the hypothesis that CYP4Z1and CYP1B1 expressions may present novel opportunities for the development of new treatments for bladder cancer. Although many studies demonstrated the aberrant expression of CYP4Z1 in many tumours, including in the breast, ovary and prostate the CYP4Z1 enzyme association with other tumours remains at the forefront of current research [4][5][6][7][8][9]28 . Our study is the rst to present convincing evidence of strong CYP4Z1 expression in different pathological subtypes of bladder cancer compared with low expression in corresponding normal tissues.…”

Section: Discussionmentioning

confidence: 99%

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Profiling of CYP4Z1 and CYP1B1 Expression in Bladder Cancers

Al-saraireh

Alshammari

Youssef

et al. 2020

Preprint

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Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes’ relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. Their expressions were significantly associated with tumour grade and stage where the expressions were markedly increased in a high grade and advanced stage of the disease ( p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging ( p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Profiling of CYP4Z1 and CYP1B1 Expression in Bladder Cancers

Al-saraireh

Alshammari

Youssef

et al. 2020

Preprint

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“…CYP4Z1 expression was shown to be highly induced in breast cancer cells by treatment with dexamethasone or progesterone [ 19 , 28 ]. This CYP4Z1 expression was translocated to the plasma membrane of breast cancer cells, while nothing displayed on the surface of normal breast cells [ 28 , 30 ]. Additionally, CYP4Z1 overexpression enhanced tumour angiogenesis, growth and spread of breast cancer cells in both in vitro and in vivo models [ 19 , 27 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Screening of cytochrome 4Z1 expression in human non-neoplastic, pre-neoplastic and neoplastic tissues

Al-saraireh

Alboaisa

Alrawashdeh

et al. 2020

ecancer

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Background: Cytochromes P450 (CYPs) constitute an enzyme family involved in the oxidative metabolism of a wide variety of endogenous and exogenous compounds, including anti-cancer drugs and carcinogens. Unlike other human CYPs, CYP4Z1 is highly expressed in human breast carcinoma and is associated with poor prognosis. As a result, CYP4Z1 was hypothesised to be a potential biomarker or drug target for the discovery and development of promising anti-cancer therapies. Materials and methods: CYP4Z1 expression was immunohistochemically studied in a set of 100 different human tissues, including normal, benign, malignant and metastatic tissues, which originated from 27 anatomical sites. As a tumour model for CYP4Z1 expression, a panel of different breast cancers was evaluated for CYP4Z1 expression and its relation to histopathological features and prognostic immunohistochemical markers. Results: The immunohistochemical results revealed that CYP4Z1 was expressed in only one (4.3%) of the normal tissues from the mammary glands, while the expression of the enzyme was positive in 1 (11%), 12 (19%) and 2 (40%) of the benign, malignant and metastatic tissues, respectively. Interestingly, several tumour entities showed prominent expressions of CYP4Z1, including carcinomas of adrenal cortex, squamous cells of oesophagus, lung and cervix, as well as seminoma, astrocytoma, melanoma and lastly endometrial adenocarcinoma. In breast cancers, CYP4Z1 was expressed in 82% of the cases. Its expression was significantly associated with the pathology of tumour, histological grade and status of lymph node metastasis. Importantly, it was also significantly associated with the expressions of Her2, P53 and Ki-67. Conclusion: These findings greatly support future plans for the use of CYP4Z1 as a biomarker or target for anti-cancer drugs. However, large-scale validation studies are needed to better delineate the potential use of CYP4Z1 for therapeutic purposes.

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“…Originally, CYP4Z1 was identified in breast tissue and noted to be upregulated in breast carcinoma (Rieger et al, 2004). In a more recent study, MCF-7 breast cancer cells exhibited aberrant CYP4Z1 protein targeted to the cell surface, and anti-CYP4Z1 autoantibodies were observed in sera of breast cancer patients, but not in that of controls (Nunna et al, 2017). CYP4Z1 expression has also been proposed as a biomarker for the existence of malignancy and/or progression of ovarian and prostate cancer (Downie et al, 2005;Tradonsky et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Expression and Functional Characterization of Breast Cancer-Associated Cytochrome P450 4Z1 inSaccharomyces cerevisiae

et al. 2017

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CYP4Z1 is an "orphan" cytochrome P450 (P450) enzyme that has provoked interest because of its hypothesized role in breast cancer through formation of the signaling molecule 20-hydroxyeicosatetraenoic acid (20-HETE). We expressed human CYP4Z1 in and evaluated its catalytic capabilities toward arachidonic and lauric acids (AA and LA). Specific and sensitive mass spectrometry assays enabled discrimination of the regioselectivity of hydroxylation of these two fatty acids. CYP4Z1 generated 7-, 8-, 9-, 10-, and 11-hydroxy LA, whereas the 12-hydroxy metabolite was not detected. HET0016, the prototypic CYP4 inhibitor, only weakly inhibited laurate metabolite formation (IC ∼15 M). CYP4Z1 preferentially oxidized AA to the 14(S),15(R)-epoxide with high regioselectivity and stereoselectivity, a reaction that was also insensitive to HET0016, but neither 20-HETE nor 20-carboxy-AA were detectable metabolites. Docking of LA and AA into a CYP4Z1 homology model was consistent with this preference for internal fatty acid oxidation. Thus, human CYP4Z1 has an inhibitor profile and product regioselectivity distinct from most other CYP4 enzymes, consistent with CYP4Z1's lack of a covalently linked heme. These data suggest that, if CYP4Z1 modulates breast cancer progression, it does so by a mechanism other than direct production of 20-HETE.

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Anti-CYP4Z1 autoantibodies detected in breast cancer patients

Cited by 31 publications

References 9 publications

Profiling of CYP4Z1 and CYP1B1 Expression in Bladder Cancers

Profiling of CYP4Z1 and CYP1B1 Expression in Bladder Cancers

Screening of cytochrome 4Z1 expression in human non-neoplastic, pre-neoplastic and neoplastic tissues

Expression and Functional Characterization of Breast Cancer-Associated Cytochrome P450 4Z1 inSaccharomyces cerevisiae

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