Site author Richard Steane
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Gene expression and cancer

Benign and malignant tumours

Although we often talk about tumours as 'growths' their formation is best explained in terms of cell division rather than growth.
A tumour - also known as a neoplasm - is a collection of cells which have grown into a defined shape. Obviously this is the result of cell division, but the speed or rate of division can be a problem, and the cell division may not be under control like ordinary cells.

Benign tumours are usually localized, and do not spread to other parts of the body. They may become surrounded by a fibrous capsule so they remain in one place within the body. However they may put pressure on nearby parts of the body as they grow in size.


A lipoma is a lump formed by a collection of fat cells, which normally form into a fairly even layer in the skin, or around body organs.

Fibroids are non-cancerous 'growths' or myomas that develop in or around the womb (uterus) during a woman's reproductive years. They are fairly spherical structures composed of fibrous and muscle tissue, and they develop in response to oestrogen, which has the effect of thickening the lining of the uterine wall as part of the menstrual cycle. They vary in size, and may not even be noticed.

Malignant tumours are cancerous growths and because their cell division is not subject to normal control they may grow quite fast and can sometimes spread to other parts of the body. This is called metastasis. Cancer cells can recur if they are not completely removed.

The five most common cancer warning signs in young people
Teenagecancertrust (44K)

Information from the Teenage Cancer Trust

Tumour suppressor genes

As their name implies, these genes normally prevent uncontrollable cell division.

However, alterations to tumour suppressor genes can lead to the development of tumours. A mutation, or (increased or abnormal) methylation, in a tumour suppressor gene may adversely affect the expression or transcription of the gene so that the amino acid sequence and hence the primary structure of its polypeptide product is altered.

This reverses its normal inhibitory action, resulting in the rapid and uncontrollable cell division which is the hallmark of cancer.

Tumour suppression is achieved via the inhibition of cell division, induction of apoptosis (cell death) to remove altered cells, DNA damage repair, and inhibition of mechanisms that cause spread of cancer cells to other parts of the body (metastasis). Some of these inhibit the transcription of specific genes required for mitosis through binding to transcription factors .


These are best explained with reference to proto-oncogenes: genes that normally control the way cells divide, grow and develop. In fact they they often code for proteins that stimulate cell division, prevent cell differentiation or regulate programmed cell death (apoptosis) within normal tissues and in this way they cause a controlled turnover of functional cells within an organ..

If a mutation occurs in the proto-oncogene, producing an oncogene, more of these proteins are produced and this leads to unregulated cell division, a slower rate of cell differentiation and increased inhibition of the normal cell death, so cells build up, causing cancer and forming a tumour.

Oncology is the study of cancer. An oncologist is a doctor who treats cancer and provides medical care for a person diagnosed with cancer.

Breast cancer

Breast cancer is the most common cancer in women, mostly women over age 50 who have been through the menopause. The NHS recommends that women who are 50 to 70 years of age should be tested for breast cancer every 3 years as part of their Breast Screening Programme.

Most cases of breast cancer do not 'run in families', but the well-known genes BRCA1 and BRCA2 can increase the risk of developing breast cancer (and also ovarian cancer). These genes may be passed on from a parent to their child.

Most women have a 12% chance of developing breast cancer in their lifetime, and women with mutated BRCA1 or BRCA2 genes may have as much as an 80% chance, and they are more likely to develop it at an early age.

The genes TP53 and CHEK2 are also associated with an increased risk of breast cancer.

The effects of oestrogen on breast cancer

Oestrogen enters target cells, and binds with a receptor protein. The activated version of this acts as a transcription factor regulating various gene expression events involved in the development of breast tissue in puberty and pregnancy.

It effectively stimulates mitosis and extra cell division. If this is uncontrolled by the mutated versions of the genes mentioned above, it results in the development of cancerous tumours. It was thought that oestrogen could act as a carcinogen in its own right but it is probably its action in increasing the number of cell divisions and thus the opportunity for random genetic errors that causes this effect.

The risk of developing breast cancer may rise slightly with the amount of oestrogen in the body. For example, having periods at a young age or later than average menopause increases the exposure to oestrogen over a longer period of time. Not having children, or having children later in life, may slightly increase the risk of developing breast cancer because exposure to oestrogen is not interrupted by pregnancy.

In postmenopausal women, circulating oestrogen concentrations are dependent on the extraglandular production of oestrogen in the adipose tissue (rather than the ovaries), which is more marked in obesity. Hormone replacement therapy (HRT) is also associated with an increased risk of developing breast cancer.

The contraceptive pill has other effects on cancer risk.
According to Cancer Research UK, taking the combined pill increases the risk of breast and cervical cancer but it decreases the risk of ovarian and womb cancers.
Evidence so far suggests the mini-pill affects the risk of breast cancer in a similar way to the combined pill. But use of progestogen-only products like the mini-pill have not been linked to ovarian cancer risk.

BRCA1 and BRCA2 genes

BRCA stands for breast cancer susceptibility gene. These are tumor suppressor genes ('caretaker genes') and they are responsible for repairing DNA, in particular double-strand breaks in DNA. They bind to damaged DNA and attract in the recombinase enzyme RAD51 which assists in this repair.

The two genes are found on different chromosomes: BRCA1 is located on chromosome 17 and BRCA2 is found on chromosome 13. Mutations in both genes increase the risk of breast, ovarian, and pancreatic cancer but BRCA1 is also involved in cervical, uterine, and colon cancers, and BRCA2 mutations also increase the risk of gall bladder, bile duct, and melanoma cancers.

Men with BRCA1 and BRCA2 mutations have a higher risk of developing breast, testicular, prostate, and pancreatic cancers.

The TP53 gene

The TP53 gene codes for a protein called tumour protein p53. Curiously, it is called the 'Guardian of the Genome'.

P53 is involved in regulating the cell cycle. It has a role in the maintenance of stem cells in the development of the embryo and throughout adult life.
If DNA is damaged, p53 can activate DNA repair proteins, and prevent the cell cycle moving on from the G1/S regulation point, allowing time for protein repair mechanisms to have an effect, or it may cause apoptosis ('programmed cell death').

Somatic mutations in the TP53 gene are much more common than inherited mutations, occurring in 20 to 40 percent of all breast cancers. Obviously somatic mutations are not passed on to the next generation in the same way that BRCA genes are.

These mutations cause changes in the p53 protein structure so it cannot regulate cell proliferation effectively. It is unable to trigger apoptosis in cells with mutated or damaged DNA. As a result, DNA damage can accumulate in cells and such cells may continue to divide in an uncontrolled way, leading to tumour growth.

The CHEK2 gene

CHEK2 (Cell cycle checkpoint kinase 2) is a tumour suppressor gene. This gene is also involved in pathways such as DNA repair, cell cycle regulation and apoptosis in response to DNA damage.

Various aberrations in the CHEK2 gene have been recorded, including 1100delC- a 'protein truncating mutation' - and I157T, R117G, I160M, G167R, G167A which are base substitutions. For instance I157T involves the substitution of isoleucine 157 by threonine.

Breast cancer in men

This is not as common as breast cancer in women, and it is normally confined to older men. Once again, oestrogen increases the risk of its development, and although men do not produce as much of this hormone as women do, this may be raised by obesity, liver conditions and genetic factors.

BRCA1 and BRCA2 genes also increase a man's chance of developing breast cancer and prostate cancer.

Other related topics on this site

(also accessible from the drop-down menu above)

This series (The control of gene expression)
Base sequence alteration
Cell potency
Regulation of transcription and translation
Gene expression and cancer

The cell cycle

Web references

Cell Cycle Control by Oncogenes and Tumor Suppressors: Driving the Transformation of Normal Cells into Cancerous Cells

Functional Mechanisms for Human Tumor Suppressors

Causes - Breast cancer in women - NHS info

Oestrogen exposure and breast cancer risk

Breast cancer in men

Does the contraceptive pill increase cancer risk?

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