Hisako Akatsuka, Tomohiro Kashikawa, Kaori Masuhara, Mizuki Tokusanai, Chenyang Li, Yumi Iida, Chisa Okada-Yamaguchi, Yoshinori Okada, Masayuki Tanaka, Takahiro Suzuki, Norio Yamamoto, Katsuto Hozumi,2025 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） AMBRA1, which was initially reported to be essential for nervous system development via autophagy and cell proliferation control, also functions as a tumor suppressor by regulating the ubiquitination of D-type cyclins through interaction with DDB1-Cullin4A/4 B E3 ligase. We had identified a missense mutation in AMBRA1 through exome analysis of a family with Cowden syndrome. The patient-type mutant showed reduced DDB1 binding and impaired cyclin D degradation. To investigate the physiological role of AMBRA1, we generated Ambra1 flox mice crossed with Rosa-Cre-ERT2-Tg mice. These inducible Ambra1 conditional knock out mice exhibited increased body weight, organ size, and enhanced S phase entry, with elevated cyclin D expression in a cell lineage- or differentiation-specific manner. Notably, their susceptibility to spontaneous, radiation-, and chemically induced malignancies was significantly higher. These findings support the role of AMBRA1 as a tumor suppressor that regulates cyclin Ds, although other targets may also contribute. DOI： 10.1016/j.isci.2025.113054 PubMed researchmap
Yu Toyoda, Akiyoshi Nakayama, Masahiro Nakatochi, Yusuke Kawamura, Hirofumi Nakaoka, Ken Yamamoto, Seiko Shimizu, Hiroshi Ooyama, Keiko Ooyama, Toru Shimizu, Mitsuo Nagase, Yuji Hidaka, Kimiyoshi Ichi2022 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Elsevier BV Despite progress in understanding of the genetic basis of gout, the precise factors affecting differences in gout susceptibility among different gout subtypes remain unclear. Using clinically diagnosed gout patients, we conducted a genome-wide meta-analysis of two distinct gout subtypes: the renal overload type and the renal underexcretion type. We provide genetic evidence at a genome-wide level of significance that supports a positive association between ABCG2 dysfunction and acquisition of the renal overload type. DOI： 10.1016/j.ymgme.2022.01.100 PubMed CiNii Research researchmap
Mathew Maria Rose, Shankar Dhamodharan, Sundaramoorthy Revathidevi, Sundaram Reddy Chakkarappan, Mani G Jagadeesan, Shanmugam Subbiah, Hirofumi Nakaoka, Ituro Inoue, Avaniyapuram Kannan Murugan, Arasa2022 · 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Elsevier BV Cervical cancer is the second most common cancer in India. The phosphatidylinositol-3 kinase (PI3K) signaling is one of the most commonly activated pathways in cancer and comprises key molecules commonly targeted in cancer therapy. This study analyzed six PI3K pathway gene mutations.We carried out targeted next-generation sequencing of six PI3K pathway genes (PIK3CA, PIK3R1, PTEN, AKT1, TSC2, and mTOR) in a total of 93 South Indian cervical cancer samples and confirmed them by sanger sequencing.The PI3K pathway gene mutations were observed in 54.8% (51/93) of the tumors and PIK3CA was the most mutated (34.4%, 32/93), followed by TSC2 (18.3%, 17/93), and PIK3R1 (14%, 13/93). The PIK3CA hotspot mutations E542K and E545K observed in this study were likely to disrupt the p110α-p85α interaction that could result in the PI3K pathway activation. We also found a few novel mutations in PIK3R1, PTEN, AKT1, TSC2, and mTOR genes while some of the tumors harbored multiple mutations in the genes of the PI3K pathway. The majority of the tumors were positive for high-risk HPV16/18 (60.7%).The high incidence of the PI3K pathway gene mutations observed in this study could be exploited for the therapeutic management of cervical cancers. DOI： 10.1016/j.cancergen.2022.05.002 PubMed CiNii Research researchmap
