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Article ; Online: Progesterone receptor-Grb2 interaction is associated with better outcomes in breast cancer.

Wittayavimol, Nattamolphan / Iwabuchi, Erina / Pateetin, Prangwan / Miki, Yasuhiro / Onodera, Yoshiaki / Sasano, Hironobu / Boonyaratanakornkit, Viroj

The Journal of steroid biochemistry and molecular biology

2023 Volume 237, Page(s) 106441

Abstract: In addition to mediating nuclear transcription, PR mediates extranuclear functions mainly through the PR polyproline domain (PPD) interaction with the SH3 domain of cytoplasmic signaling molecules. PR-PPD-SH3 interaction inhibits EGF-mediated signaling ... ...

Abstract	In addition to mediating nuclear transcription, PR mediates extranuclear functions mainly through the PR polyproline domain (PPD) interaction with the SH3 domain of cytoplasmic signaling molecules. PR-PPD-SH3 interaction inhibits EGF-mediated signaling and decreases lung cancer cell proliferation. Grb2 is an essential adaptor molecule with an SH2 domain flanked by two SH3 domains. In this study, we examined whether PR, through interaction between PR-PPD and Grb2-SH3, can interact with Grb2 in cells and breast cancer tissues. Our previous study shows that interaction between PR-PPD and Grb2 could interfere with cytoplasmic signaling and lead to inhibition of EGF-mediated signaling. GST-pulldown analysis shows that PR-PPD specifically interacts with the SH3 domains of Grb2. Immunofluorescence staining shows colocalization of PR and Grb2 in both the nucleus and cytoplasm in BT-474 breast cancer cells. Using Bimolecular Fluorescence Complementation (BiFC) analysis, we show that PR and Grb2 interact in breast cancer cells through the Grb2-SH3 domain. Proximity Ligation Assay (PLA) analysis of 43 breast cancer specimens shows that PR-Grb2 interaction is associated with low histological stage and negatively correlates with lymph node invasion and metastasis in breast cancer. These results, together with our previous findings, suggest that PR-PPD interaction with Grb2 plays an essential role in PR-mediated growth factor signaling inhibition and could contribute significantly to better prognosis in PR- and Grb2-positive breast cancer. Our finding provides a basis for additional studies to explore a novel therapeutic strategy for cancer treatment.
MeSH term(s)	Humans ; Female ; Receptors, Progesterone/genetics ; Breast Neoplasms/genetics ; Epidermal Growth Factor ; Progesterone ; Signal Transduction/physiology ; Protein Binding
Chemical Substances	Receptors, Progesterone ; Epidermal Growth Factor (62229-50-9) ; Progesterone (4G7DS2Q64Y)
Language	English
Publishing date	2023-12-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2023.106441
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Article ; Online: SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.

Tsunokake, Satoko / Iwabuchi, Erina / Miki, Yasuhiro / Kanai, Ayako / Onodera, Yoshiaki / Sasano, Hironobu / Ishida, Takanori / Suzuki, Takashi

Breast cancer research and treatment

2023 Volume 201, Issue 3, Page(s) 499–513

Abstract: Purpose: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained ... ...

Abstract	Purpose: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro. Methods: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors. Results: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation. Conclusion: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.
MeSH term(s)	Humans ; Female ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Sodium-Glucose Transporter 2/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Glucose/metabolism ; Carcinoma, Ductal
Chemical Substances	Sodium-Glucose Transporter 2 Inhibitors ; Sodium-Glucose Transporter 2 ; Vascular Endothelial Growth Factor A ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-07-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-023-07024-9
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Article ; Online: Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells.

Yamaguchi, Mio / Takagi, Kiyoshi / Narita, Koki / Miki, Yasuhiro / Onodera, Yoshiaki / Miyashita, Minoru / Sasano, Hironobu / Suzuki, Takashi

International journal of molecular sciences

2021 Volume 22, Issue 4

Abstract: Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, ... ...

Abstract	Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Chemokine CCL5/metabolism ; Disease Progression ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local/metabolism ; Paracrine Communication ; Prognosis ; Receptors, CCR1/metabolism ; Receptors, CCR3/metabolism ; Receptors, CCR5/metabolism ; Signal Transduction ; Stromal Cells/metabolism ; Tumor Microenvironment
Chemical Substances	CCL5 protein, human ; CCR1 protein, human ; CCR3 protein, human ; CCR5 protein, human ; Chemokine CCL5 ; Receptors, CCR1 ; Receptors, CCR3 ; Receptors, CCR5
Language	English
Publishing date	2021-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22041918
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Article: Forkhead Box I1 in Breast Carcinoma as a Potent Prognostic Factor.

Onodera, Yoshiaki / Takagi, Kiyoshi / Neoi, Yoshimi / Sato, Ai / Yamaguchi, Mio / Miki, Yasuhiro / Ebata, Akiko / Miyashita, Minoru / Sasano, Hironobu / Suzuki, Takashi

Acta histochemica et cytochemica

2021 Volume 54, Issue 4, Page(s) 123–130

Abstract: Forkhead box (FOX) proteins are family of transcriptional factors and regulate cell growth and differentiation as well as embryogenesis and longevity. Previous studies have demonstrated that several FOX members regulate growth or metastasis of breast ... ...

Abstract	Forkhead box (FOX) proteins are family of transcriptional factors and regulate cell growth and differentiation as well as embryogenesis and longevity. Previous studies have demonstrated that several FOX members regulate growth or metastasis of breast carcinoma, but clinical significance of total FOX members remains unclear. We first examined associations between expression of 40 FOX genes and TNM status of 19 breast carcinoma using microarray data. Subsequently, we immunolocalized FOXI1 in 140 breast carcinomas and evaluated its clinicopathological significance. In the microarray analysis, we newly identified that gene expression of FOXI1 was most pronouncedly linked to metastasis of the breast carcinoma among the FOX members examined. However, clinicopathological significance of FOXI1 has not been examined in the breast carcinoma. FOXI1 immunoreactivity was positive in 44 out of 140 (31%) of breast carcinomas, and it was significantly associated with stage, lymph node metastasis and distant metastasis. The FOXI1 status was significantly associated with worse prognosis of the breast cancer patients, and it turned out to be an independent prognostic factor for both distant disease-free survival and breast cancer-specific survival. These findings suggest that FOXI1 plays important roles in the metastasis of breast carcinoma and immunohistochemical FOXI1 status is a potent prognostic factor.
Language	English
Publishing date	2021-07-31
Publishing country	Japan
Document type	Journal Article
ZDB-ID	280005-6
ISSN	1347-5800 ; 0044-5991
ISSN (online)	1347-5800
ISSN	0044-5991
DOI	10.1267/ahc.21-00034
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Article ; Online: Androgens enhance the ability of intratumoral macrophages to promote breast cancer progression.

Yamaguchi, Mio / Takagi, Kiyoshi / Sato, Masayasu / Sato, Ai / Miki, Yasuhiro / Onodera, Yoshiaki / Miyashita, Minoru / Sasano, Hironobu / Suzuki, Takashi

Oncology reports

2021 Volume 46, Issue 3

Abstract: Androgens are produced locally in breast carcinoma tissues by androgen‑producing enzymes such as 5α‑reductase type 1 (5αRed1) and affect not only breast cancer cells but the tumor microenvironment as well. Tumor‑associated macrophages (TAMs) are primary ... ...

Abstract	Androgens are produced locally in breast carcinoma tissues by androgen‑producing enzymes such as 5α‑reductase type 1 (5αRed1) and affect not only breast cancer cells but the tumor microenvironment as well. Tumor‑associated macrophages (TAMs) are primary components of the tumor microenvironment and contribute to tumor progression. Although previous studies suggest that androgen/androgen receptor (AR) signaling in macrophages has important roles in human diseases, androgen action on TAMs has remained largely unknown. We immunolocalized macrophage marker CD163 as well as AR and 5αRed1 in 116 breast carcinomas and correlated them with clinicopathological parameters and clinical outcomes. Moreover, we examined the roles of androgens on macrophages in breast cancer progression using cell lines 4T1 (mouse breast cancer) and RAW264.7 (macrophage) in a tumor‑bearing female BALB/c mouse model. Double immunohistochemistry revealed that AR was sporadically expressed in the macrophages in breast carcinoma tissues. Macrophage infiltration was significantly correlated with an aggressive phenotype of breast carcinomas and worse prognosis, especially in the 5αRed1‑positive group. In a sphere‑forming assay using 4T1 and RAW‑AR cells, which stably express AR, the sphere size was significantly increased due to androgens when 4T1 cells were cocultured with RAW‑AR cells. Furthermore,
MeSH term(s)	3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics ; Androgens/metabolism ; Animals ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation ; Coculture Techniques ; Disease Progression ; Female ; Humans ; Macrophages/metabolism ; Membrane Proteins/genetics ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Phenotype ; RAW 264.7 Cells ; Tumor-Associated Macrophages/metabolism
Chemical Substances	Androgens ; Membrane Proteins ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (EC 1.3.99.5) ; SRD5A1 protein, human (EC 1.3.99.5)
Language	English
Publishing date	2021-07-19
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2021.8139
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Zs.A 4213: Show issues

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Article: In Situ

Iwabuchi, Erina / Miki, Yasuhiro / Ono, Katsuhiko / Onodera, Yoshiaki / Sasano, Hironobu

Acta histochemica et cytochemica

2017 Volume 50, Issue 2, Page(s) 85–93

Abstract: The estrogen receptor (ER) functions as a dimer and is involved in several different biological functions. However ER dimeric proteins have not been identified ... ...

Abstract	The estrogen receptor (ER) functions as a dimer and is involved in several different biological functions. However ER dimeric proteins have not been identified by
Language	English
Publishing date	2017-04-22
Publishing country	Japan
Document type	Journal Article
ZDB-ID	280005-6
ISSN	1347-5800 ; 0044-5991
ISSN (online)	1347-5800
ISSN	0044-5991
DOI	10.1267/ahc.17011
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Article ; Online: ARHGAP15 in Human Breast Carcinoma: A Potent Tumor Suppressor Regulated by Androgens.

Takagi, Kiyoshi / Miki, Yasuhiro / Onodera, Yoshiaki / Ishida, Takanori / Watanabe, Mika / Sasano, Hironobu / Suzuki, Takashi

International journal of molecular sciences

2018 Volume 19, Issue 3

Abstract: Rho GTPase activating protein 15 (ARHGAP15) is a recently identified GTPase activating protein which enhances intrinsic hydrolysis of GTP-bound Ras-related C3 botulinus toxin substrate (Rac1), resulting in inactivation of Rac1. Although a lot of studies ... ...

Abstract	Rho GTPase activating protein 15 (ARHGAP15) is a recently identified GTPase activating protein which enhances intrinsic hydrolysis of GTP-bound Ras-related C3 botulinus toxin substrate (Rac1), resulting in inactivation of Rac1. Although a lot of studies have pointed out the pivotal roles of the Rac1 pathway in the progression of breast carcinomas, the clinical significance of ARHGAP15 has remained largely unknown in human breast carcinomas. Therefore, we immunolocalized ARHGAP15 in one hundred breast carcinoma tissues. ARHGAP15 immunoreactivity was frequently detected in the cytoplasm of carcinoma cells, and was positively correlated with that of Rac1 and androgen receptor labeling index. Furthermore, ARHGAP15 immunoreactivity was significantly correlated with decreased risk of recurrence and improved prognosis, and multivariate analyses demonstrated that ARHGAP15 immunoreactivity was an independent prognostic factor for both disease-free and breast-cancer-specific survival of the patients. In addition, exogenous overexpression of ARHGA15 suppressed cell proliferation and migration of MCF-7 cells and SK-BR-3 cells. On the other hand,
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Androgens/pharmacology ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Carcinoma/genetics ; Carcinoma/metabolism ; Carcinoma/pathology ; Cell Movement ; Cell Proliferation ; Cytoplasm/metabolism ; Dihydrotestosterone/pharmacology ; Female ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/metabolism ; Humans ; MCF-7 Cells ; Middle Aged ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Up-Regulation/drug effects
Chemical Substances	ARHGAP15 protein, human ; Androgens ; Biomarkers, Tumor ; GTPase-Activating Proteins ; RNA, Messenger ; Dihydrotestosterone (08J2K08A3Y)
Language	English
Publishing date	2018-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms19030804
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Article ; Online: The crosstalk between aldosterone and calcium metabolism in primary aldosteronism: A possible calcium metabolism-associated aberrant "neoplastic" steroidogenesis in adrenals.

Gao, Xin / Yamazaki, Yuto / Tezuka, Yuta / Onodera, Yoshiaki / Ogata, Hiroko / Omata, Kei / Morimoto, Ryo / Nakamura, Yasuhiro / Satoh, Fumitoshi / Sasano, Hironobu

The Journal of steroid biochemistry and molecular biology

2019 Volume 193, Page(s) 105434

Abstract: Intracellular calcium (Ca) levels play pivotal roles in aldosterone biosynthesis. Several somatic mutations of ion channels associated with aldosterone over-production were reported to result in over-inflow of Ca ion. Recently, the main regulators of ... ...

Abstract	Intracellular calcium (Ca) levels play pivotal roles in aldosterone biosynthesis. Several somatic mutations of ion channels associated with aldosterone over-production were reported to result in over-inflow of Ca ion. Recently, the main regulators of extracellular Ca including VDR, CaSR and PTH1R were also reported to regulate steroidogenesis including aldosterone production. Therefore, not only intracellular but also extracellular Ca levels could regulate aldosterone biosynthesis. In addition, primary aldosteronism (PA) is clinically associated with not only more frequent cardiovascular events but also secondary metabolic disorders including abnormal calcium metabolism, osteoporosis and others. However, the details of Ca metabolic abnormalities associated with, including the potential correlation between those abnormalities and aldosterone overproduction, have remained virtually unknown. Therefore, in this study, we first immunolocalized Ca metabolism-related receptors (CaSR, VDR and PTH1R) in normal adrenal glands (NAs), aldosterone-producing adenomas (APAs) and cortisol-producing adenoma (CPA). We then compared the findings with clinicopathological parameters of these patients and the patterns of KCNJ5 somatic mutation of the tumors among APA patients. In vitro study was also performed to further explore the potential effects of extracellular Ca, PTH, Vitamin D and ionophore on aldosterone production. Ca metabolism-related receptors were predominantly localized in aldosterone-producing cells (ZG and APA) in both immunohistochemistry and qRT-PCR analysis. CYP11B2 mRNA was significantly increased by CaCl
MeSH term(s)	Adrenal Cortex Neoplasms/genetics ; Adrenal Cortex Neoplasms/metabolism ; Adrenal Glands/metabolism ; Adrenocortical Adenoma/genetics ; Adrenocortical Adenoma/metabolism ; Adult ; Aged ; Aldosterone/metabolism ; Calcium/metabolism ; Cell Line, Tumor ; Cytochrome P-450 Enzyme System/genetics ; Female ; Humans ; Hyperaldosteronism/genetics ; Hyperaldosteronism/metabolism ; Male ; Middle Aged ; Receptor, Parathyroid Hormone, Type 1/metabolism ; Receptors, Calcitriol/metabolism ; Receptors, Calcium-Sensing/metabolism ; Young Adult
Chemical Substances	CASR protein, human ; PTH1R protein, human ; Receptor, Parathyroid Hormone, Type 1 ; Receptors, Calcitriol ; Receptors, Calcium-Sensing ; VDR protein, human ; Aldosterone (4964P6T9RB) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-07-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2019.105434
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Article ; Online: The significance of lipid accumulation in breast carcinoma cells through perilipin 2 and its clinicopathological significance.

Kuniyoshi, Shimpei / Miki, Yasuhiro / Sasaki, Akari / Iwabuchi, Erina / Ono, Katsuhiko / Onodera, Yoshiaki / Hirakawa, Hisashi / Ishida, Takanori / Yoshimi, Naoki / Sasano, Hironobu

Pathology international

2019 Volume 69, Issue 8, Page(s) 463–471

Abstract: Both systemic and intratumoral lipid metabolism have been recently reported to play pivotal roles in both tumor development and progression in various human malignancies including breast cancer. However, its details have remained largely unknown in ... ...

Abstract	Both systemic and intratumoral lipid metabolism have been recently reported to play pivotal roles in both tumor development and progression in various human malignancies including breast cancer. However, its details have remained largely unknown in breast cancer patients. Therefore, in this study, we focused on perilipin 2, which is involved in constituting the intracellular lipid composition. Perilipin 2 was first immunolocalized in 105 cases of breast cancer. The status of perilipin 2 immunoreactivity was significantly positively associated with histological grade, Ki-67 labeling index and HER2 status and negatively with estrogen receptor status of these patients. Subsequent in vitro study also revealed that its mRNA expression in triple negative breast carcinoma cells was higher than cells of other subtypes. We then examined the correlation between perilipin 2 immunoreactivity and intracellular lipid droplet evaluated by Oil-red O stating in 13 cases of breast carcinoma tissues. A significantly positive correlation was detected between the status of perilipin 2 and Oil-red O staining. These findings above did indicate that perilipin 2 could represent the status of intracellular lipid droplets in surgical pathology specimens of breast cancer and perilipin 2 was also associated with its more aggressive biological phenotypes.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/diagnosis ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/diagnosis ; Carcinoma, Lobular/metabolism ; Carcinoma, Lobular/pathology ; Cell Line, Tumor ; Female ; Humans ; Lipid Metabolism ; Middle Aged ; Neoplasm Invasiveness ; Perilipin-2/metabolism
Chemical Substances	Biomarkers, Tumor ; PLIN2 protein, human ; Perilipin-2
Language	English
Publishing date	2019-07-04
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1194850-4
ISSN	1440-1827 ; 1320-5463
ISSN (online)	1440-1827
ISSN	1320-5463
DOI	10.1111/pin.12831
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Article ; Online: Co-expression of carcinoembryonic antigen-related cell adhesion molecule 6 and 8 inhibits proliferation and invasiveness of breast carcinoma cells.

Iwabuchi, Erina / Miki, Yasuhiro / Onodera, Yoshiaki / Shibahara, Yukiko / Takagi, Kiyoshi / Suzuki, Takashi / Ishida, Takanori / Sasano, Hironobu

Clinical & experimental metastasis

2019 Volume 36, Issue 5, Page(s) 423–432

Abstract: The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 and CEACAM8 form heterodimers and exert their effects. Therefore, we examined the effects of CEACAM6 and CEACAM8 co-expression in breast cancer. We first studied CEACAM6/8 expression ... ...

Abstract	The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 and CEACAM8 form heterodimers and exert their effects. Therefore, we examined the effects of CEACAM6 and CEACAM8 co-expression in breast cancer. We first studied CEACAM6/8 expression using immunohistochemistry in 109 patients with breast cancer. We then established MCF-7 cells that were stably transfected with CEACAM8 and studied cell proliferation, invasion and adhesion. The number of CEACAM6 and CEACAM8 double-positive breast carcinoma cells significantly increased in patients with low histopathological grade and stage. Proximity ligation assay (PLA) confirmed high CEACAM6/8 expression in MCF-7 cells. CEACAM6/8 expression promoted the adhesion of MCF-7 cells to endothelial cell monolayers but inhibited their invasion and proliferation. Furthermore, CEACAM6 status in carcinoma cells was significantly higher in bone than in lung metastases. CEACAM6/8 expression is associated with the inhibition of vascular invasion and cell proliferation. CEACAM6 expression was also considered to be involved in bone metastases of breast cancer. This is the first study to demonstrate the possible role of CEACAM6/8 heterodimer and CEACAM6 expression in breast cancer patients.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antigens, CD/metabolism ; Apoptosis ; Biomarkers, Tumor/metabolism ; Bone Neoplasms/metabolism ; Bone Neoplasms/secondary ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Adhesion Molecules/metabolism ; Cell Proliferation ; Female ; Follow-Up Studies ; GPI-Linked Proteins/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/metabolism ; Lung Neoplasms/secondary ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Tumor Cells, Cultured
Chemical Substances	Antigens, CD ; Biomarkers, Tumor ; CEACAM6 protein, human ; CEACAM8 protein, human ; Cell Adhesion Molecules ; GPI-Linked Proteins
Language	English
Publishing date	2019-06-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604952-7
ISSN	1573-7276 ; 0262-0898
ISSN (online)	1573-7276
ISSN	0262-0898
DOI	10.1007/s10585-019-09981-2
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Full text online

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Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito