表皮生长因子受体对PI3K/AKT通路失调在犬类软组织肉瘤的潜在贡献
Alfarisa Nururrozi1,2, Masaya Igase1,3, Kyohei Miyanishi1
1Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
In vivo (Athens, Greece)
|December 31, 2024
概括
过度表达EGFR,而不是PTEN损失或PIK3CA突变,可能会驱动狗软组织肉瘤 (STS) 中的PI3K/AKT通路. 需要进一步的研究来证实这些发现在狗STS.
科学领域:
- 兽医瘤学 兽医瘤学
- 分子病理学分子病理学
- 狗癌症研究 狗癌症研究
背景情况:
- 软组织肉瘤 (STS) 是狗中常见的一种介质细胞瘤.
- 酸丁醇-3激酶 (PI3K) /蛋白激酶B (AKT) 途径在犬类STS中经常被激活.
- 驱动这种通路激活的特定分子机制尚未完全理解.
研究的目的:
- 研究PTEN损失,PIK3CA突变和EGFR过度表达在犬类STS中的PI3K/AKT通路激活中的作用.
- 为了确定犬类STS的潜在治疗点.
主要方法:
- 对36只狗的STS样本进行分析.
- 对于PTEN和EGFR表达的免疫组织化学.
- 对PIK3CA和EGFR突变进行DNA测序.
主要成果:
- 没有观察到PTEN损失;然而,在33.3%的样本中存在弱的PTEN表达.
- 在一个样本中发现了一个单一的PIK3CA突变;没有发现热点突变.
- 高EGFR表达与高酸-AKT水平 (p<0.0001) 有很强的相关性,83.3%的样本显示EGFR阳性,90%的样本也显示酸-AKT阳性.
结论:
- 过度表达EGFR似乎是犬类STS中PI3K/AKT通路失调的重要因素.
- 失去PTEN和PIK3CA突变是不太可能的贡献者.
- 需要进行更大规模的研究来验证这些发现,并探索针对犬类STS的EGFR的治疗策略.
相关概念视频
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K
03:03mTOR Signaling and Cancer Progression
3.7K
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...
The mTOR pathway or the...
3.7K
02:38Mitogens and the Cell Cycle
6.4K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
02:23Abnormal Proliferation
4.4K
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...
4.4K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K