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HIF2A and IGF2 in Neuroblastoma and Small Cell Lung Carcinoma

Johansson, Erik (2013) MOBM15 20121
Degree Projects in Molecular Biology
Abstract
Abstract

Neuroblastoma is the third most common form of cancer to strike children, after brain tumours and leukemia. It is highly diverse and advanced tumours are difficult to treat, with high mortality rates, although some advanced tumours spontaneously regress.

Lung Cancer is the most common cancer in the world and a leading cause of cancer related deaths worldwide. It is classified into Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC), where SCLC is more aggressive and has a higher mortality rate than NSCLC.

Hypoxia is a feature of almost all solid tumours and something both normal and transformed cells have the ability to endure and adapt to. As a tumour outgrows the capacity for its accompanying... (More)
Abstract

Neuroblastoma is the third most common form of cancer to strike children, after brain tumours and leukemia. It is highly diverse and advanced tumours are difficult to treat, with high mortality rates, although some advanced tumours spontaneously regress.

Lung Cancer is the most common cancer in the world and a leading cause of cancer related deaths worldwide. It is classified into Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC), where SCLC is more aggressive and has a higher mortality rate than NSCLC.

Hypoxia is a feature of almost all solid tumours and something both normal and transformed cells have the ability to endure and adapt to. As a tumour outgrows the capacity for its accompanying blood vessels to supply oxygen, hypoxia initially serves to limit the growth of the tumour. However, as the tumour cells adapt to low oxygen pressures they often become more aggressive and prone to metastasize.

The Hypoxia Inducible Factor (HIF) proteins are key regulators of the cellular response to hypoxia and if activated, can induce many of the changes that make advanced tumours dangerous and difficult to treat. In this report, we show that the NSCLC cell line U1810 have similar HIF2A and IGF2 mRNA expression patterns as the neuroblastoma cell lines SK-N-BE(2)c and KCN-69n, with low HIF2A and IGF2 expression at 21% oxygen (normoxia) and high expression at 1% oxygen (hypoxia). We also show that the SCLC cell line U1690 and the neuroblastoma cell line IMR-32 have very low expression of HIF2A and IGF2 mRNA at 21% oxygen and 1% oxygen, both at acute and prolonged phases of hypoxia. Despite their different HIF expression patterns, both U1810 and U1690 have a functioning PI3K-AKT pathway, as suggested by the presence of phosphorylated AKT. (Less)
Abstract
Popular science summary

Cancer is a disease of growth. The cancerous cells have lost the ability to stop themselves from growing and dividing. They often grow so fast that they can't get enough oxygen, the blood vessels can't keep up with their demand. We call this hypoxia.
One might think this is a good thing, we don't want cancers to grow unchecked. But our cells have ways to deal with oxygen starvation and cancer cells do too. While a tumor often stops growing when it gets too big, sometimes it find ways to keep growing and can become more aggresive and more prone to spread to other parts of the body. For cancer, surviving hypoxia and coaxing more blood vessels to grow and deliver more oxygen, are important steps in the progression... (More)
Popular science summary

Cancer is a disease of growth. The cancerous cells have lost the ability to stop themselves from growing and dividing. They often grow so fast that they can't get enough oxygen, the blood vessels can't keep up with their demand. We call this hypoxia.
One might think this is a good thing, we don't want cancers to grow unchecked. But our cells have ways to deal with oxygen starvation and cancer cells do too. While a tumor often stops growing when it gets too big, sometimes it find ways to keep growing and can become more aggresive and more prone to spread to other parts of the body. For cancer, surviving hypoxia and coaxing more blood vessels to grow and deliver more oxygen, are important steps in the progression of the disease.
In my master's thesis, I investigated how some of these steps happen. I grew cells from neuroblastoma, a rather nasty childhood cancer, and cells from two types of lung cancer in a hypoxia chamber. I looked at the activity of a few genes that are important in the cell's response to hypoxia, so called hypoxia induced factors or HIFs. I found that the activity of one of these HIFs was linked to the activity of an important growth factor, called IGF 2. This growth factor is involved in many processes including the growth of new blood vessels. When the activity of the HIF went up so did the activity of IGF 2, when it went down, IGF 2's activity also went down. Whether this HIF caused IGF 2 to become more active or if it is the other way round, I can't tell. I also don't know if this happens in other types of cancer.
Reasearch is often a slow process. Each experiment can take a long time do and cost quite a lot of money. Often what you get from them is not groundbreaking discoveries but simple data that, if you're lucky, you can piece together to form a single fact, one piece of the puzzle. I feel quite priviledged that I could help find this tiny little piece and that one day my research can help save people from this terrible disease. (Less)
Please use this url to cite or link to this publication:
author
Johansson, Erik
supervisor
organization
course
MOBM15 20121
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
4146902
date added to LUP
2013-11-12 11:54:43
date last changed
2013-11-12 11:54:43
@misc{4146902,
  abstract     = {Popular science summary

Cancer is a disease of growth. The cancerous cells have lost the ability to stop themselves from growing and dividing. They often grow so fast that they can't get enough oxygen, the blood vessels can't keep up with their demand. We call this hypoxia.
One might think this is a good thing, we don't want cancers to grow unchecked. But our cells have ways to deal with oxygen starvation and cancer cells do too. While a tumor often stops growing when it gets too big, sometimes it find ways to keep growing and can become more aggresive and more prone to spread to other parts of the body. For cancer, surviving hypoxia and coaxing more blood vessels to grow and deliver more oxygen, are important steps in the progression of the disease.
In my master's thesis, I investigated how some of these steps happen. I grew cells from neuroblastoma, a rather nasty childhood cancer, and cells from two types of lung cancer in a hypoxia chamber. I looked at the activity of a few genes that are important in the cell's response to hypoxia, so called hypoxia induced factors or HIFs. I found that the activity of one of these HIFs was linked to the activity of an important growth factor, called IGF 2. This growth factor is involved in many processes including the growth of new blood vessels. When the activity of the HIF went up so did the activity of IGF 2, when it went down, IGF 2's activity also went down. Whether this HIF caused IGF 2 to become more active or if it is the other way round, I can't tell. I also don't know if this happens in other types of cancer.
Reasearch is often a slow process. Each experiment can take a long time do and cost quite a lot of money. Often what you get from them is not groundbreaking discoveries but simple data that, if you're lucky, you can piece together to form a single fact, one piece of the puzzle. I feel quite priviledged that I could help find this tiny little piece and that one day my research can help save people from this terrible disease.},
  author       = {Johansson, Erik},
  language     = {eng},
  note         = {Student Paper},
  title        = {HIF2A and IGF2 in Neuroblastoma and Small Cell Lung Carcinoma},
  year         = {2013},
}