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Gene Expression in Breast Carcinomas: Pathogenesis (Hormone Sensitive)

Two types of estrogen receptors, ERα and ERβ, exist with ERα playing a clear role in breast carcinogenesis. When estrogen binds to the ER, the complex enters the nucleus and induces transcription of proteins that lead to cell proliferation. Estrogen's proliferative effects can negatively impact patients with high levels of these receptors. Two hypotheses for estrogen's role in breast cancer are its genotoxic metabolites causing DNA damage and its hormonal effects promoting proliferation of cancerous and pre-cancerous cells. Overexpression of the HER2 proto-oncogene, which forms clusters in breast tumor cell membranes, is associated with rapid tumor growth and poorer health outcomes, though its carcinogenic mechanism is unknown.

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Nadira Farah Prayogo
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41 views3 pages

Gene Expression in Breast Carcinomas: Pathogenesis (Hormone Sensitive)

Two types of estrogen receptors, ERα and ERβ, exist with ERα playing a clear role in breast carcinogenesis. When estrogen binds to the ER, the complex enters the nucleus and induces transcription of proteins that lead to cell proliferation. Estrogen's proliferative effects can negatively impact patients with high levels of these receptors. Two hypotheses for estrogen's role in breast cancer are its genotoxic metabolites causing DNA damage and its hormonal effects promoting proliferation of cancerous and pre-cancerous cells. Overexpression of the HER2 proto-oncogene, which forms clusters in breast tumor cell membranes, is associated with rapid tumor growth and poorer health outcomes, though its carcinogenic mechanism is unknown.

Uploaded by

Nadira Farah Prayogo
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Pathogenesis (hormone sensitive)

 N Engl J Med. 2006 Jan 19;354(3):270-82.


 Oncologist. 2003;8(4):307-25.

Gene expression in breast carcinomas


Two different types of estrogen receptors exist, alpha (α) and beta (β) (ERα and ERβ respectively). Various
tissues express these receptors with breast, ovaries and the endometrium expressing ERα, while the kidneys,
brain, lungs and several other organs expressing ERβ. The role of ERβ in carcinogenesis remains controversial
whereas, a clear contribution of ERα protein has been established.

Both ER subtypes carry a DNA binding domain and exist in the nucleus and the cytosol. When estrogen enters
the cell, it binds the ER and the complex migrates into the nucleus and leads to the production of transcription
proteins that induces changes in the cell. Therefore, due to estrogen’s proliferative properties, its cellular
stimulation can have negative consequences in patients expressing large quantities of these receptors
intracellularly.

Role of estrogen in breast cancer progression and development


Two major hypotheses attempt to explain the tumorigenic effects of estrogen: (i) genotoxic effects of estrogen
metabolites via generation of radicals (initiator) and (ii) the hormonal properties of estrogen inducing
proliferation of cancers as well as the premalignant cells (promoter).

Role of Human Epidermal Growth Factor Receptor 2 (HER2)


HER2 belongs to the epidermal growth factor receptor (EGFR) family of proto-oncogenes and currently is not
known to have a ligand. However, the protein has been shown to form clusters within the cell membranes in
malignant breast tumours. Its mechanism of carcinogenesis remains largely unknown, but overexpression is
associated with rapid tumour growth, shortened survival, increased risk of recurrence after surgery, and poor
response to conventional chemotherapeutic agents.
http://www.pathophys.org/breast-cancer/

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