Co-expression of the Hypoxic Marker Carbonic Anhydrase 9 (CA-IX) with Breast Cancer Associated 1 (BRCA1) is associated with faster recurrence in High Grade Serous Adenocarcinoma

2017 ◽  
Vol 147 (1) ◽  
pp. 199
Author(s):  
A. Krieg ◽  
P. Mwahech-Fauceglia ◽  
J. Lim ◽  
T. Pejovic
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
High Grade ◽  
Serous Adenocarcinoma ◽  
Ca Ix ◽  
Carbonic Anhydrase 9

scholarly journals A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells

2019 ◽  
Vol 476 (10) ◽  
pp. 1497-1513 ◽  
Author(s):  
Mam Y. Mboge ◽  
Zhijuan Chen ◽  
Daniel Khokhar ◽  
Alyssa Wolff ◽  
Lingbao Ai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Extracellular Ph ◽  
Carbonic Anhydrase Ix ◽  
Monocarboxylate Transporter ◽  
Proton Efflux ◽  
Ca Ix

AbstractThe most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production. This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt. We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here, we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression. Yet, isoform-selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation. Other investigators have suggested the CA IX co-operates with the MCT transport family to excrete protons. To test this possibility, we examined the expression patterns of selected ion transporters and show that members of this family are differentially expressed within the molecular subtypes of breast cancer. The most aggressive form of breast cancer, triple-negative breast cancer, appears to co-ordinately express the monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX). This supports a possible mechanism that utilizes the intramolecular H+ shuttle system in CA IX to facilitate proton efflux through MCT4.

scholarly journals Carbonic anhydrase 9 is associated with chemosensitivity and prognosis in breast cancer patients treated with taxane and anthracycline

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Naoki Aomatsu ◽  
Masakazu Yashiro ◽  
Shinichiro Kashiwagi ◽  
Hidemi Kawajiri ◽  
Tsutomu Takashima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Carbonic Anhydrase 9

Prognostic Significance of a Novel Hypoxia-Regulated Marker, Carbonic Anhydrase IX, in Invasive Breast Carcinoma

2001 ◽  
Vol 19 (16) ◽  
pp. 3660-3668 ◽  
Author(s):  
Stephen K. Chia ◽  
Charles C. Wykoff ◽  
Peter H. Watson ◽  
Cheng Han ◽  
Russell D. Leek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Breast Carcinoma ◽  
Carbonic Anhydrase ◽  
Invasive Breast Cancer ◽  
Estrogen Receptor Status ◽  
Prognostic Significance ◽  
Invasive Breast Carcinoma ◽  
Carbonic Anhydrase Ix ◽  
Ca Ix

PURPOSE: To assess the frequency of expression and the prognostic significance of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of patients with invasive breast cancer. PATIENTS AND METHODS: CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treated with adjuvant hormonal or chemotherapy. The frequency of CA IX expression, its association with recognized prognostic factors, and the relationship with outcome was evaluated by univariate and multivariate statistical analyses. RESULTS: CA IX expression was present in 49 (48%) of 103 cases. The level of CA IX expression was found to be significantly associated with tumor necrosis (P < .001), higher grade (P = .02), and negative estrogen receptor status (P < .001). Furthermore, CA IX expression was associated with a higher relapse rate (P = .004) and a worse overall survival (P = .001). By multivariate analysis, CA IX was also shown to be an independent predictive factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to 6.75, P = .05). CONCLUSION: CA IX expression was associated with worse relapse-free survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.

scholarly journals Betulin Sulfonamides as Carbonic Anhydrase Inhibitors and Anticancer Agents in Breast Cancer Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8808
Author(s):  
Antje Güttler ◽  
Yvonne Eiselt ◽  
Anne Funtan ◽  
Andreas Thiel ◽  
Marina Petrenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Carbonic Anhydrase ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Clonogenic Survival ◽  
Breast Cancer Cell Lines ◽  
Protein Levels ◽  
Ca Ix

Hypoxia-regulated protein carbonic anhydrase IX (CA IX) is up-regulated in different tumor entities and correlated with poor prognosis in breast cancer patients. Due to the radio- and chemotherapy resistance of solid hypoxic tumors, derivatives of betulinic acid (BA), a natural compound with anticancer properties, seem to be promising to benefit these cancer patients. We synthesized new betulin sulfonamides and determined their cytotoxicity in different breast cancer cell lines. Additionally, we investigated their effects on clonogenic survival, cell death, extracellular pH, HIF-1α, CA IX and CA XII protein levels and radiosensitivity. Our study revealed that cytotoxicity increased after treatment with the betulin sulfonamides compared to BA or their precursors, especially in triple-negative breast cancer (TNBC) cells. CA IX activity as well as CA IX and CA XII protein levels were reduced by the betulin sulfonamides. We observed elevated inhibitory efficiency against protumorigenic processes such as proliferation and clonogenic survival and the promotion of cell death and radiosensitivity compared to the precursor derivatives. In particular, TNBC cells showed benefit from the addition of sulfonamides onto BA and revealed that betulin sulfonamides are promising compounds to treat more aggressive breast cancers, or are at the same level against less aggressive breast cancer cells.

770 poster PROGNOSTIC SIGNIFICANCE OF CARBONIC ANHYDRASE IX (CA IX) IN BREAST CANCER PATIENTS TREATED WITH RADIOTHERAPY

2011 ◽  
Vol 99 ◽  
pp. S303-S304
Author(s):  
L. Beketic-Oreskovic ◽  
P. Ozretic ◽  
Z. Rabbani ◽  
I. Jackson ◽  
B. Sarcevic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Carbonic Anhydrase Ix ◽  
Breast Cancer Patients ◽  
Ca Ix

scholarly journals The Expression of Carbonic Anhydrase (CA) IX/XII and Lymph Node Metastasis in Early Breast Cancer

2016 ◽  
Vol 48 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Keun-Yong Eom ◽  
Min Hye Jang ◽  
So Yeon Park ◽  
Eun Young Kang ◽  
Sung Won Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Carbonic Anhydrase ◽  
Early Breast Cancer ◽  
Node Metastasis ◽  
Ca Ix

Prognostic Significance of Carbonic Anhydrase IX (CA-IX), Endoglin (CD105) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in Breast Cancer Patients

2011 ◽  
Vol 17 (3) ◽  
pp. 593-603 ◽  
Author(s):  
Lidija Beketic-Oreskovic ◽  
Petar Ozretic ◽  
Zahid N. Rabbani ◽  
Isabel L. Jackson ◽  
Bozena Sarcevic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Carbonic Anhydrase Ix ◽  
Breast Cancer Patients ◽  
Ca Ix

scholarly journals Influence of Paclitaxel and Doxorubicin Therapy of ßIII-Tubulin, Carbonic Anhydrase IX, and Survivin in Chemically Induced Breast Cancer in Female Rat

2021 ◽  
Vol 22 (12) ◽  
pp. 6363
Author(s):  
Alena Pastornická ◽  
Silvia Rybárová ◽  
Slávka Drahošová ◽  
Jozef Mihalik ◽  
Andrea Kreheľová ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Effective Means ◽  
Survivin Expression ◽  
Carbonic Anhydrase Ix ◽  
Fisher Exact Test ◽  
Female Rat ◽  
Exact Test ◽  
Ca Ix ◽  
Chemically Induced

Breast cancer is the most common cancer in females. The aim of this study was to determine the effect of paclitaxel (PTX) and doxorubicin (DOX) therapy on the βIII-tubulin, carbonic anhydrase IX (CA IX), and survivin expression in chemically-induced rat mammary tumors. Animals with induced mammary carcinogenesis were randomly divided into treatment groups and an untreated group. The total proportion of tumors, the proportion of carcinoma in situ (CIS), and invasive carcinoma (IC) were evaluated. Protein expression in tumor tissue was determined using IHC. Statistical analysis of the data, evaluated by Fisher-exact test and unpaired t-test. Significantly increased levels of proteins in the tumor cells were confirmed using the IHC method for all studied proteins. The expression of βIII-tubulin, CA IX, and survivin increased significantly after treatment with both cytostatics (PTX and DOX). Depending on the type of tumor, a significant increase in all proteins was observed in IC samples after PTX treatment, and CA IX expression after DOX treatment. In CIS samples, a significant increase of βIII-tubulin and survivin expression was observed after a DOX treatment. The results suggest that βIII-tubulin, survivin, and CA IX may be significant drug resistance markers and the clinical regulation of their activity may be an effective means of reversing this resistance.

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