関連する実験動画

Updated: Feb 24, 2026

Modeling Breast Cancer via an Intraductal Injection of Cre-expressing Adenovirus into the Mouse Mammary Gland

Modeling Breast Cancer via an Intraductal Injection of Cre-expressing Adenovirus into the Mouse Mammary Gland

Published on: June 7, 2019

ER陰性およびHER2陽性乳癌におけるアポクリン分化を伴うPIK3CA変異

Fumi Nozaki¹, Yoko Nakanishi², Yukari Hirotani²

¹Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173- 8610, Japan. fuchinoue.fumi@nihon-u.ac.jp.

Breast cancer (Tokyo, Japan)

|February 23, 2026

要旨

Background:

Targeted therapies for PIK3CA-mutated breast cancer are currently limited to the hormone receptor (HR)-positive and HER2-negative subtype. Carcinoma with apocrine differentiation (apocrine ca.) is typically characterized as ER-negative and HER2-positive/negative. Consequently, patients with apocrine ca. are generally excluded from PIK3CA genotyping and targeted therapies, even when mutations are present. Here, we investigated the prevalence and functional significance of PIK3CA mutations in apocrine ca., particularly in ER-negative (HER2-subtypes and triple-negative) subtypes.

Methods:

We analyzed hotspot PIK3CA mutations in apocrine ca. and invasive breast carcinoma of no special type (IBC-NST) (20 and 70 samples, respectively). PIK3CA knockdown was performed to compare the proliferation of breast cancer cell lines representing two types of apocrine ca. with PIK3CA mutations (MDA-MB-453: ER-/HER2+/AR + and MFM223: ER-/HER2-/AR+) and one without PIK3CA mutations (HCC1428: ER+/HER2-/AR-).

Results:

PIK3CA mutations occurred in apocrine ca. (3/20, 15.0%) and IBC-NST (2/70, 2.9%) cases (P = 0.071). Within the ER-negative and HER2-positive subtypes, PIK3CA mutations were present in 25% of apocrine ca. (2/8) cases, whereas no mutations were observed in positive IBC-NST (0/18) (P = 0.086). siRNA-mediated PIK3CA knockdown reduced the proliferation of MDA-MB-453 (P < 0.01) and MFM223 (P = 0.01) cells, whereas no effect was observed in HCC1428 cells (P = 0.674), relative to the non-targeting siRNA control.

Conclusions:

PIK3CA mutations are present in ER-negative and HER2-positive apocrine ca., and these mutations drive PIK3CA-dependent proliferation in vitro. These results suggest that patients with apocrine ca. may benefit from PIK3CA mutation testing and subsequent targeted therapy.

キーワード:

乳癌アポクリン分化を伴う癌腫 PI3K PIK3CA

さらに関連する動画

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Published on: August 1, 2018

High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts

High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts

Published on: December 20, 2024

関連する概念動画

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...

Tumor Progression

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...

Cancers Originate from Somatic Mutations in a Single Cell

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...