HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer

被引：30

作者：

Hosonaga, Mari ^{[1
]}

Arima, Yoshimi ^{[2
]}

Sampetrean, Oltea ^{[2
]}

Komura, Daisuke ^{[3
]}

Koya, Ikuko ^{[4
]}

Sasaki, Takashi ^{[5
]}

Sato, Eiichi ^{[6
]}

Okano, Hideyuki ^{[4
]}

Kudoh, Jun ^{[7
]}

Ishikawa, Shumpei ^{[3
]}

Saya, Hideyuki ^{[2
]}

Ishikawa, Takashi ^{[1
]}

机构：

[1] Tokyo Med Univ, Dept Breast Surg & Oncol, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan

[2] Keio Univ, Inst Adv Med Res, Div Gene Regulat, Sch Med,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[3] Tokyo Med & Dent Univ, Med Res Inst, Dept Genom Pathol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan

[4] Keio Univ, Dept Physiol, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[5] Keio Univ, Ctr Supercentenarian Med Res, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[6] Tokyo Med Univ, Inst Med Sci, Dept Pathol, Med Res Ctr,Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan

[7] Keio Univ, Lab Gene Med, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 08期

关键词：

HER2; heterogeneity; breast cancer; poor prognosis; caspase-1; GENE AMPLIFICATION; INTRATUMORAL HETEROGENEITY; CELLS; CARCINOMAS; EXPRESSION; CASPASE-1; EVOLUTION; IMPACT;

D O I：

10.3390/ijms19082158

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported in 16-36% of HER2-positive breast cancer and its clinical impact is under discussion. We examined the biological effects of HER2-heterogeneity on mouse models and analyzed metastatic brains by RNA sequence analysis. A metastatic mouse model was developed using 231-Luc (triple negative cells) and 2 HER2-positive cell lines, namely, HER2-60 and HER2-90 which showed heterogeneous and monotonous HER2 expressions, respectively. Metastatic lesions developed in 3 weeks in all the mice injected with HER2-60 cells, and in 69% of the mice injected with HER2-90 and 87.5% of the mice injected with 231-Luc. The median survival days of mice injected with 231-Luc, HER2-60, and HER2-90 cells were 29 (n = 24), 24 (n = 22) and 30 (n = 13) days, respectively. RNA sequence analysis showed that CASP-1 and its related genes were significantly downregulated in metastatic brain tumors with HER2-60 cells. The low expression of caspase-1 could be a new prognostic biomarker for early relapse in HER2-positive breast cancer.

引用

页数：12

共 50 条

[31] HER2 amplification by next-generation sequencing to identify HER2-positive invasive breast cancer with negative HER2 immunohistochemistry
Morsberger, Laura
Pallavajjala, Aparna
Long, Patty
Hardy, Melanie
Park, Rebecca
Parish, Rebecca
Nozari, Azin
Zou, Ying S.
CANCER CELL INTERNATIONAL, 2022, 22 (01)
[32] High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer
Tanei, Tomonori
Seno, Shigeto
Sota, Yoshiaki
Hatano, Takaaki
Kitahara, Yuri
Abe, Kaori
Masunaga, Nanae
Tsukabe, Masami
Yoshinami, Tetsuhiro
Miyake, Tomohiro
Shimoda, Masafumi
Matsuda, Hideo
Shimazu, Kenzo
CANCERS, 2024, 16 (05)
[33] Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer
Nafi, Siti Norasikin Mohd
Generali, Daniele
Kramer-Marek, Gabriela
Gijsen, Merel
Strina, Carla
Cappelletti, Mariarosa
Andreis, Daniele
Haider, Syed
Li, Ji-Liang
Bridges, Esther
Capala, Jacek
Ioannis, Roxanis
Harris, Adrian L.
Kong, Anthony
ONCOTARGET, 2014, 5 (15) : 5934 - 5949
[34] HER2 heterogeneity and treatment response- associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial
Li, Zheqi
Metzger Filho, Otto
Viale, Giuseppe
dell'Orto, Patrizia
Russo, Leila
Goyette, Marie -Anne
Kamat, Avni
Yardley, Denise A.
Abramson, Vandana Gupta
Arteaga, Carlos L.
Spring, Laura M.
Chiotti, Kami
Halsey, Carol
Waks, Adrienne G.
King, Tari A.
Lester, Susan C.
Bellon, Jennifer R.
Winer, Eric P.
Spellman, Paul T.
Krop, Ian E.
Polyak, Kornelia
JOURNAL OF CLINICAL INVESTIGATION, 2024, 134 (07)
[35] The Adjuvant Treatment of HER2-Positive Breast Cancer
Jelovac, Danijela
Wolff, Antonio C.
CURRENT TREATMENT OPTIONS IN ONCOLOGY, 2012, 13 (02) : 230 - 239
[36] Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer
Sonnenblick, Amir
Salmon-Divon, Mali
Salgado, Roberto
Dvash, Efrat
Ponde, Noam
Zahavi, Tamar
Salmon, Asher
Loibl, Sibylle
Denkert, Carsten
Joensuu, Heikki
Ameye, Lieveke
Van den Eynden, Gert
Kellokumpu-Lehtinen, Pirkko-Liisa
Azaria, Amos
Loi, Sherene
Michiels, Stefan
Richard, Francois
Sotiriou, Christos
INTERNATIONAL JOURNAL OF CANCER, 2020, 147 (01) : 266 - 276
[37] Ten-year survival of neoadjuvant dual HER2 blockade in patients with HER2-positive breast cancer
Nuciforo, Paolo
Townend, John
Piccart, Martine J.
Fielding, Shona
Gkolfi, Panagiota
El-Abed, Sarra
de Azambuja, Evandro
Werutsky, Gustavo
Bliss, Judith
Moebus, Volker
Colleoni, Marco
Aspitia, Alvaro Moreno
Gomez, Henry
Gombos, Andrea
Coccia-Portugal, Maria A.
Tseng, Ling-Ming
Kunz, Georg
Lerzo, Guillermo
Sohn, Joohyuk
Semiglazov, Vladimir
Saura, Cristina
Kroep, Judith
Ferro, Antonella
Cameron, David
Gelber, Richard
Huober, Jens
Di Cosimo, Serena
EUROPEAN JOURNAL OF CANCER, 2023, 181 : 92 - 101
[38] Genetic heterogeneity of HER2 in breast cancer: impact on HER2 testing and its clinicopathologic significance
Yang, Yi-ling
Fan, Yu
Lang, Rong-gang
Gu, Feng
Ren, Mei-Jing
Zhang, Xin-Min
Yin, Dong
Fu, Li
BREAST CANCER RESEARCH AND TREATMENT, 2012, 134 (03) : 1095 - 1102
[39] In situ detection of HER2:HER2 and HER2:HER3 protein-protein interactions demonstrates prognostic significance in early breast cancer
Spears, Melanie
Taylor, Karen J.
Munro, Alison F.
Cunningham, Carrie A.
Mallon, Elizabeth A.
Twelves, Chris J.
Cameron, David A.
Thomas, Jeremy
Bartlett, John M. S.
BREAST CANCER RESEARCH AND TREATMENT, 2012, 132 (02) : 463 - 470
[40] Disulfiram targets cancer stem-like properties and the HER2/Akt signaling pathway in HER2-positive breast cancer
Kim, Ji Young
Cho, Youngkwan
Oh, Eunhye
Lee, Nahyun
An, Hyunsook
Sung, Daeil
Cho, Tae-Min
Seo, Jae Hong
CANCER LETTERS, 2016, 379 (01) : 39 - 48

← 1 2 3 4 5 →