Novel roles of adipocytes in the mammary gland development and breast cancer progression, and involvement of adipokines in the roles

• Project/Area Number: 21380177
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: Hokkaido University
• Principal Investigator: KIMURA Kazuhiro 北海道大学, 大学院・獣医学研究科, 教授 (30192561)
• Co-Investigator(Kenkyū-buntansha): OKAMATSU Yoko 北海道大学, 大学院・獣医学研究科, 助教 (90527178)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 乳腺 / 乳癌 / 脂肪細胞 / エストロゲン / プロラクチン / レプチン / HGF / NGF / 乳腺発達 / プロゲステロン / STAT / 母性行動 / ストレス / 脳機能 / 肥満 / 泌乳

Research Abstract

The mammary gland develops in subcutaneous adipose tissue in the post natal period, and adipocytes function as a nursing cell for epithelial cells. With hypertrophy of adipocytes, ductal development of mammary gland in non-pregnant mice was impaired. Hypertrophy of adipocytes also delayed side-branch formation from the duct in the early phase of pregnancy, and acinar formation and its maturation in the mid-and late phase of pregnancy. Hypertrophy of adipocytes caused hyper-leptinemia, and leptin mimicked some effects by hypertrophy of adipocytes both in vivo and in vitro. Therefore, it was suggested that hypertrophy of adipocytes suppressed mammary gland development and leptin partly played a role in the suppression.

Research Products

• [Journal Article] Implications for C-peptide-cell membrane interaction (2012)
  • Author(s): Ishii, T., Fukano, K., Shimada, K., Kamikawa, A., Okamatsu-Ogura Y., Terao, A., Yoshida, T., Saito, , M and Kimura, K.
  • Journal Title: J. Biochem. Pages: 1-1
• [Journal Article] Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes (2012)
  • Author(s): Shimada, K., Ohno, Y., Okamatsu-Ogura, Y., Suzuki, M., Kamikawa, A., Terao, A. and Kimura, K
  • Journal Title: Peptides Volume: 34 Pages: 336-342
  • NAID: 120004066090
  • Peer Reviewed
• [Journal Article] Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes (2012)
  • Author(s): Shimada, K., et al.
  • Journal Title: Peptides Volume: 34 Issue: 2 Pages: 336-336
  • DOI: 10.1016/j.peptides.2012.02.012
  • Peer Reviewed
• [Journal Article] Possible involvement of uncoupling protein 1 in appetite control by leptin (2011)
  • Author(s): Okamatsu-Ogura, Y., Nio-Kobayashi, J., Iwanaga, T., Terao, A., Kimura, K. and Saito M.
  • Journal Title: Exp Biol Med Volume: 236 Pages: 1274-1281
  • NAID: 120003614971
  • Peer Reviewed
• [Journal Article] Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation (2011)
  • Author(s): Shimba, S., Ogawa, T., Hitosugi, S., Ichihashi, Y., Nakadaira, Y., Kobayashi, M., Tezuka, M., Kosuge, Y., Ishige, K., Ito, Y., Komiyama, K., Okamatsu-Ogura, Y., Kimura, K. and Saito, M.
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation (2011)
  • Author(s): Shimba, S., et al.
  • Journal Title: PLoS ONE Volume: 6 Issue: 9 Pages: e25231-e25231
  • DOI: 10.1371/journal.pone.0025231
  • Peer Reviewed
• [Journal Article] Possible involvement of uncoupling protein 1 in appetite control by leptin (2011)
  • Author(s): Okamatsu-Ogura, Y., et al.
  • Journal Title: Exp Biol Med Volume: 236 Issue: 11 Pages: 1274-1274
  • DOI: 10.1258/ebm.2011.011143
  • Peer Reviewed
• [Journal Article] Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype (2010)
  • Author(s): Sawada, T., Miyoshi, H., Shimada, K., Suzuki, A., Okamatsu, Y., Perfield II, J. W., Kondo, T., Nagai, S., Shimizu, C., Yoshioka, N., Greenberg, A. S., Kimura, K. and Koike, T.
  • Journal Title: PLoS ONE
  • NAID: 120002646887
  • Peer Reviewed
• [Journal Article] Effects of retinoic acid and hydrogen peroxide on sterol regulatory element-binding protein-la activation during adipogenic differentiation of 3T3-L1 cells (2010)
  • Author(s): Abd Eldaim, M. A., Okamatsu-Ogura, Y., Terao, A., and Kimura, K.
  • Journal Title: Jpn. J. Vet. Res. Volume: 58 Pages: 149-154
  • Peer Reviewed
• [Journal Article] Retinol binding protein 4 in dairy cows : its presence in colostrum and alteration in plasma during fasting, inflammation, and the peripartum period. (2010)
  • Author(s): Abd Eldaim, M. A., Kamikawa, A., Soliman, M. M., Ahmed, M. M., Okamatsu-Ogura, Y., Terao, A., Miyamoto, T. and Kimura, K.
  • Journal Title: J. Dairy Res Volume: 77 Pages: 27-32
  • NAID: 120002725529
  • Peer Reviewed
• [Journal Article] Proinsulin C-peptide prevents Type-1 diabetes-induced decrease of renal Na^+-K^+-ATPase α1-subunit in rats. (2010)
  • Author(s): Nordquist, L., Shimada, K., Ishii, T., Furuya, D.T., Kamikawa, A. and Kimura, K.
  • Journal Title: Diab. Metab. Res. Rev Volume: 26 Pages: 193-199
  • Peer Reviewed
• [Journal Article] Retinol binding protein 4 in dairy cows : its presence in colostrum and alteration in plasma during fasting, inflammation, and the peripartum period. (2010)
  • Author(s): Abd Eldaim, M.A., et al.
  • Journal Title: J.Dairy Res. Volume: 77 Pages: 27-32
  • Peer Reviewed
• [Journal Article] Effects of retinoic acid and hydrogen peroxide on sterol regulatory element-binding protein-1a activation during adipogenic differentiation of 3T3-L1 cells. (2010)
  • Author(s): Abd Eldaim, M.A., et al.
  • Journal Title: Jpn.J.Vet.Res. Volume: 58 Pages: 149-154
  • Peer Reviewed
• [Journal Article] Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype. (2010)
  • Author(s): Sawada, T., et al.
  • Journal Title: PLoS ONE
  • Peer Reviewed
• [Journal Article] 褐色脂肪細胞によるエネルギー代謝制御におけるPGC-1の役割 (2009)
  • Author(s): 岡松優子、木村和弘
  • Journal Title: 内分泌・糖尿病科 Volume: 29 Pages: 109-116
• [Journal Article] 食餌性肥満が乳腺発達に及ぼす影響 (2009)
  • Author(s): 上川昭博、鈴木千春、山本敦子、木村和弘
  • Journal Title: 肥満研究 Volume: 15 Pages: 222-224
  • NAID: 10026150208
• [Journal Article] Proinsulin Ceptide induces cun N-terminal kinase 1 expression in LEII mouse lung capillary endothelial cells. (2009)
  • Author(s): Furuya, D. T., Ishii, T., Kamikawa, A., Shimada, K., Machado, U.F., Saito, M. and Kimura, K
  • Journal Title: Jpn. J. Vet. Res Volume: 57 Pages: 163-167
  • Peer Reviewed
• [Journal Article] Role of protease inhibitors and acylation stimulating protein in the adipogenesis in 3T3-L1 cells. (2009)
  • Author(s): Soliman, M. M, El-Senosi, Y. A.-F., Salem, M. M., Hamid, O. M. A., and Kimura K.
  • Journal Title: J. Vet. Sci Volume: 10 Pages: 197-201
  • Peer Reviewed
• [Journal Article] Diet induced obesity disrupts ductal development in the mammary glands of nonpregnant mice (2009)
  • Author(s): Kamikawa, A., Ichii, O., Yamaji, D., Imao, T., Suzuki, C., Okamatsu-Ogura, Y., Terao, A., Kon, Y. and Kimura, K.
  • Journal Title: Dev. Dyn Volume: 238 Pages: 1092-1099
  • Peer Reviewed
• [Journal Article] Feline adiponectin : molecular structures and plasma concentrations in obese cats. (2009)
  • Author(s): Ishioka, K., Omachi, A., Sasaki, N., Kimura, K., and Saito, M.
  • Journal Title: J. Vet. Med. Sci Volume: 71 Pages: 189-194
  • NAID: 110007109596
  • Peer Reviewed
• [Journal Article] Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice. (2009)
  • Author(s): Kamikawa, A., et.al.
  • Journal Title: Dev.Dyn. 238 Pages: 1092-1099
  • Peer Reviewed
• [Journal Article] Role of protease inhibitors and acylation stimulating protein in the adipogenesis in 3T3-L1 cells. (2009)
  • Author(s): Soliman, M.M., et al.
  • Journal Title: J.Vet.Sci. 10 Pages: 197-201
  • Peer Reviewed
• [Journal Article] Feline adiponectin : molecular structures and plasma concentrations in obese cats. (2009)
  • Author(s): Ishioka, K., et al.
  • Journal Title: J.Vet.Med.Sci. 71 Pages: 189-194
  • Peer Reviewed
• [Presentation] C-peptide modulates alpha-enolase activity (2011)
  • Author(s): Kimura, K.
  • Organizer: 欧州糖尿病学会
  • Place of Presentation: Feira Internacional de Lisboa(ポルトガル)
  • Year and Date: 2011-09-12
• [Presentation] 脂肪細胞特異的p27Kip1発現マウスでは褐色脂肪組織の形成が著しく抑制される (2011)
  • Author(s): 岡松優子、阪上浩、寺尾晶、斉藤昌之、木村和弘
  • Organizer: 第48回日本生化学会北海道支部例会
  • Place of Presentation: 札幌医科大学記念ホール(札幌)
  • Year and Date: 2011-08-05
• [Presentation] Adiponectin inhibits nerve growth factor function through their direct interaction. (2011)
  • Author(s): Kazuhiro Kimura, Yuu Okura, Akihiro Kamikawa, Yuko Okamatsu-Ogura, Akira Terao.
  • Organizer: The 47th EASD Annual Meeting
  • Place of Presentation: Lisbon, Portugal
• [Presentation] The role of UCP1 in the regulation of energy metabolism (2011)
  • Author(s): Yuko Okamatsu-Ogura, Akira Terao, Kazuhiro Kimura, Masayuki Saito
  • Organizer: The lth Brown Adipose Tissue
  • Place of Presentation: Update, Sapporo, Japan
• [Presentation] Possible roles of neuropeptide Y in the regulation of brown adipose tissue functions (2011)
  • Author(s): Kouhei Shimada, Yuko Okamatsu, Akira Terao, Kazuhiro Kimura
  • Organizer: The 1th Brown Adipose Tissue 2011 Update
  • Place of Presentation: Sapporo, Japan
• [Presentation] Diet-induced obesity disrupts postnatal and pregnancy-associated mammary gland development in mice : possible roles of leptin (2010)
  • Author(s): Kimura, K., et al.
  • Organizer: XI International Conference on Obesity
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2010-07-12
• [Presentation] 食餌性肥が睡眠に及ぼす影響 (2010)
  • Author(s): 丹野翔伍、寺尾晶、岡松優子、木村和弘
  • Organizer: 日本肥満学会
  • Place of Presentation: 前橋テルサ(群馬)
• [Presentation] 食餌性肥満はマウスの母性行動に影響する (2010)
  • Author(s): 山本敦子、上川昭博、鈴木千春、加藤千絵子、岡松優子、寺尾晶、木村和弘
  • Organizer: 日本肥満学会
  • Place of Presentation: 前橋テルサ(群馬)
• [Presentation] Diet-induced obesity disrupts postnatal and pregnancy-assosiated mammary gland development in mice : possible roles of leptin. (2010)
  • Author(s): Kimura, K. Kamikawa, A. Suzuki, C. Yamamoto, A.
  • Organizer: The International Association for the Study of Obesity (ICO2010)
  • Place of Presentation: Stockholm, Sweden
• [Presentation] マブルクアティアアブドゥルダイムレチノイン酸の脂肪蓄積抑制作用は高グルコースにより解除される (2010)
  • Author(s): 木村和弘
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテルグランヴィア岡山(岡山)
• [Presentation] Diet-induced obesity disrupts postnatal and pregnancy induced mammary development in mice : Possible roles of leptin (2010)
  • Author(s): Akihiro Kamikawa, Chiharu Suzuki, Atsuko Yamamoto, Yuko Okamatsu, Akira Terao, Kazuhiro Kimura
  • Organizer: The 14th International Congress of Endocrinology (ICE2O1O)
  • Place of Presentation: Kyoto, Japan
• [Presentation] Thermogenic UCP1 enhances anorexigenic effect of leptin in mice. (2010)
  • Author(s): Yuko Okamatsu, Akira Terao, Kazuhiro Kimura, Masayuki Saito
  • Organizer: The 14th International Congress of Endocrinology (ICE2O1O)
  • Place of Presentation: Kyoto, Japan
• [Presentation] 肥満症と睡眠障害の病態関連を調べる (2010)
  • Author(s): 寺尾晶、丹野翔伍、酒井紀彰、岡松優子、木村和弘
  • Organizer: 第149回日本獣医学会学術集会
  • Place of Presentation: 日本獣医生命科学大学(東京)
• [Presentation] 肥満の成因・病態とビタミンAによる脂肪量の調節 (2010)
  • Author(s): 木村和弘
  • Organizer: 第149回日本獣医学会学術集会
  • Place of Presentation: 日本獣医生命科学大学(東京)
• [Presentation] 肥満の成因・病態とビタミンAによる脂肪量の調節 (2010)
  • Author(s): 木村和弘
  • Organizer: 第149回日本獣医学会(シンポジュウム)
  • Place of Presentation: 日本獣医生命科学大学(東京都)
• [Presentation] 秦葉繁紀時計遺伝子BrainandMuscleArntlikeprotein 1(BMAL1)1こよるエネルギー代謝制御 (2009)
  • Author(s): 中平裕基、岡松優子、木村和弘、斉藤昌之
  • Organizer: 第14回アディポサイエンス研究会シンポジウム
  • Place of Presentation: 千里阪急ホテル(大阪)
  • Year and Date: 2009-08-22
• [Presentation] 秦葉繁紀時計遺伝子BrainandMuscleArntlikeprotein1(BMAL1)1こよる脂肪組織ペントースリ酸回路の調節 (2009)
  • Author(s): 一杉俊輔、市橋裕也、岡松優子、木村和弘、斉藤昌之
  • Organizer: 第14回アディポサイエンス研究会シンポジウム
  • Place of Presentation: 千里阪急ホテル(大阪)
  • Year and Date: 2009-08-22
• [Presentation] 血管内皮細胞におけるNPY新規シグナル伝達分子としての転写因子STAT3 (2009)
  • Author(s): 島田光平、岡松優子、寺尾晶、木村和弘
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫)
• [Presentation] Effects of retinoic acid on lipid accumulation in bovine and mouse adipocytes are inverted dependently on glucose concentration in the cultures (2009)
  • Author(s): Abd El Daim Mabrouk, Mohamed Ahmed, 岡松優子,上川昭博,寺尾晶,木村和弘
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: とりぎん文化会館(鳥取)
• [Presentation] Thermogenic UCP1 controls appetite through modulation of leptin sensitivity. (2009)
  • Author(s): Okamatsu-Ogura, Y. , Terao, A. , Kimura, K. , Saito, M.
  • Organizer: The 3rd international symposium on physiology and pharmacology of temperature regulation
  • Place of Presentation: くにびきメッセ(島根)
• [Presentation] プロインスリンCペプチド受容体同定の試み (2009)
  • Author(s): 石井辰矢、岡松優子、寺尾晶、木村和弘
  • Organizer: 第147回日本獣医学会学術集会
  • Place of Presentation: 栃木県総合文化センター(栃木)
• [Presentation] Quantification of retinol bindinig protein 4 (RBP4) level in cow plasma and milk and its relation to retinol concentration (2009)
  • Author(s): Mabrouk Abd El Daim,上川昭博,寺尾晶,木村和弘
  • Organizer: 第147回日本獣医学会学術集会
  • Place of Presentation: 栃木県総合文化センター(栃木)
• [Presentation] 肥満による細胞外基質形成の異常と乳腺組織構築の阻害 (2009)
  • Author(s): 上川昭博、鈴木千春、木村和弘
  • Organizer: 第147回日本獣医学会学術集会
  • Place of Presentation: 栃木県総合文化センター(栃木)
• [Book] In:Sima AAF (ed) Diabetes and C-Peptide:Scientific and Clinical Aspects. Contemporary Diabetes (2012)
  • Author(s): Kimura, K. and Kamikawa, A
  • Publisher: Is NO-eNOS a target for C?peptide action and its protective effects on diabetic nephropathy?
• [Book] UCPと酸素消費量、からだと酸素の辞典 (2009)
  • Author(s): 木村和弘
  • Publisher: (酸素ダイナミックス研究会編、朝倉書店)3章
• [Remarks]
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  • URL: http://www.vetmed.hokudai.ac.jp/
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