ARHGAP15 in Human Breast Carcinoma: A Potent Tumor Suppressor Regulated by Androgens.

Tytuł:: ARHGAP15 in Human Breast Carcinoma: A Potent Tumor Suppressor Regulated by Androgens.
Autorzy:: Takagi K; Departments of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Miyagi-ken, Sendai 980-8575, Japan. .
Miki Y; Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science, Tohoku University, Sendai, Miyagi 980-8574, Japan. .
Onodera Y; Departments of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan. .
Ishida T; Departments of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. .
Watanabe M; Department of Pathology, Tohoku University Hospital, Sendai, Miyagi 980-8574, Japan. .
Sasano H; Departments of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan. .; Department of Pathology, Tohoku University Hospital, Sendai, Miyagi 980-8574, Japan. .
Suzuki T; Departments of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Miyagi-ken, Sendai 980-8575, Japan. .
Źródło:: International journal of molecular sciences [Int J Mol Sci] 2018 Mar 10; Vol. 19 (3). Date of Electronic Publication: 2018 Mar 10.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:: Androgens/*pharmacology
Biomarkers, Tumor/*metabolism
Breast Neoplasms/*genetics
Carcinoma/*genetics
Dihydrotestosterone/*pharmacology
GTPase-Activating Proteins/*metabolism
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Carcinoma/metabolism ; Carcinoma/pathology ; Cell Movement ; Cell Proliferation ; Cytoplasm/metabolism ; Female ; GTPase-Activating Proteins/genetics ; Humans ; MCF-7 Cells ; Middle Aged ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Up-Regulation/drug effects
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Contributed Indexing:: Keywords: ARHGAP15; Rac1; androgens; breast carcinoma; immunohistochemistry
Substance Nomenclature:: 0 (ARHGAP15 protein, human)
0 (Androgens)
0 (Biomarkers, Tumor)
0 (GTPase-Activating Proteins)
0 (RNA, Messenger)
08J2K08A3Y (Dihydrotestosterone)
Entry Date(s):: Date Created: 20180315 Date Completed: 20180827 Latest Revision: 20181114
Update Code:: 20240105
PubMed Central ID:: PMC5877665
DOI:: 10.3390/ijms19030804
PMID:: 29534468
: Czasopismo naukowe

Pełny tekst

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, ARHGAP15 mRNA was significantly induced by dihydrotestosterone. These findings suggest that ARHGAP15 is an androgen-induced gene and has anti-tumorigenic roles associated with the Rac1 pathway. ARHGAP15 immunoreactivity is therefore considered a potent prognostic factor in human breast carcinomas.
Competing Interests: The authors declare no conflict of interest.

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