HORMONES IN CANCER

1. HORMONES
IN
CANCER
Presented by
Sruthi Purushothaman
IInd Semester MSc. Biotechnology

2. Some hormones cause cancer, primarily by
encouraging cell proliferation
Important cause of sex-related cancers
such as cancer of the breast, endometrium,
prostate, ovary, and testis, and also of
thyroid cancer and bone cancer
An individual's hormone levels are mostly
determined genetically
Men of African ancestry have significantly
higher levels of testosterone than men of
European ancestry, and have a
correspondingly much higher level of
prostate cancer

3. Non-genetic factors are also relevant:
 Obese people have higher levels of some hormones
associated with cancer
 Women who take hormone replacement therapy have a
higher risk of developing cancers
 People who exercise far more than average have lower
levels of these hormones, and lower risk of cancer
 Osteosarcoma may be caused by growth hormones

4. • SST and GHRH control GH
production
• In blood GH activates the
production of IGF1 and IGF2
by liver and bind to IGFBPs
• IGF1 and IGF2 are ligands for
IGF1R, tyrosine kinase
receptor that signals
proliferative and anti-
apoptotic pathways in breast
and prostate cells
• IGF2R binds IGF2, is not
known to have tyrosine-
kinase activity and might
negatively regulate
proliferation by reducing the
binding of IGF2 to IGF1R
IGF SIGNALLING PATHWAY IN CELL
SIGNALLING AND SURVIVAL

5. • Reguates sex-hormone-binding globulin
(SHBG) synthesis
• Stimulates steroid hormone synthesis in
ovarian and testicular tissue
IGF ALSO….

6. Sex steroid hormones, inflammation and cancer
• In the liver, a carcinogen
(diethylnitrosamine, DEN) causes tissue
damage and activates the MyD88–NF-B
signalling pathway in Kupffer cells
• These cells produce IL-6 which in turn
promotes inflammation, tissue damage, cell
proliferation and tumour formation
• Oestrogens interfere with NF-B activity and
IL-6 production, so females tend to be
protected against liver cancer
• Zhu et al. - in prostate cancer, macrophage-
derived IL-1 converts an androgen-receptor
antagonist (Steroid Androgen Receptor
Modulator, SARM) into an agonist that
stimulates gene transcription.
• The molecular sensor for the IL-1
inflammatory signals is TAB2, which on
phosphorylation releases the TAB2/N-
CoR/HDAC repressor complex from the gene
promoter, activating gene transcription.
• An SARM is thus converted from a tumour
inhibitor to a tumour promoter.

7. • Exogenous administration of specific
hormones, particularly steroid hormones, or
drugs which inhibit the production or activity
of such hormones (hormone antagonist)
• Because steroid hormones are powerful
drivers of gene expression in certain cancer
cells, changing the levels or activity of certain
hormones can cause certain cancers to cease
growing, or even undergo cell death
• Used for several types of cancers derived
from hormonally responsive tissues - breast,
prostate, endometrium, and adrenal cortex
• Most familiar example of hormonal therapy in
oncology is the use of the selective estrogen-
response modulator tamoxifen for the
treatment of breast cancer
HORMONE THERAPY

8. • Antagonist of the estrogen receptor in breast
tissue via its active metabolite,
hydroxytamoxifen-competitive antagonism
• Nonsteroidal agent
• Agonist in endometrium-Mixed
agonist/antagonist
TAMOXIFEN
•A report in September 2009 from Health and
Human Services' Agency for Healthcare
Research and Quality - side effects
•Endometrial cancer
•American Cancer Society lists tamoxifen as a
known carcinogen

9. Bioidentical hormones and hormone replacement therapy
• Exact same molecular structure as the
hormones made by a woman’s body
• Synthetic hormone is created in a lab to
be different from anything found in nature
so that it can be patented
• Synthetic progesterone is called a
progestin
• E3N French Women Prospective Study
2008-women using synthetic HRT had a
60% higher risk of cancer, while women
using bioidenticals still had the same risk
as women using no HRT of any kind
• Association of natural progesterone with
estrogens confers less or even no risk of
breast cancer as opposed to the use of
synthetic progestins
• The conclusion of the French E3N study is
that bioidentical hormones do not
increase the risk of breast cancer

10. • IPT is an alternative medicine pharmacologic strategy
for the chemotherapy of cancer using insulin and
low-dose chemotherapy
• 3 main functions:
INSULIN POTENTIATION THERAPY
Differentiation between cancerous and normal cells
Modification of cancer cell metabolism
Increase in cell membrane permeability

11. DIFFERENTIATION BETWEEN CANCEROUS AND NORMAL CELLS
• Based on insulin receptor concentration
• Cancer cells have developed the ability to
produce insulin and IGF themselves; this
way they can autonomously increase their
glucose uptake
• Cancer cells have a much higher
concentration of receptors
• An added boost- insulin is able to react
with its own receptors and is also cross-
react with and activate the IGF receptors
on cancer cells. Thus insulin will affect
cancer cells more strongly than normal
tissues
• By activating the insulin and IGF receptors
on cancer cells through IPT treatment, the
biological differences of cancer cells can be
highlighted – a vital consideration for the
safety of cancer chemotherapy

12. Modification of cancer cell metabolism
• The standard chemotherapy involves drugs, which are designed to attack
rapidly dividing cells
• Unfortunately hair cells, RBCs ,WBCs and cells found in the digestive tract
are also rapidly dividing cells - the reason for various side effects
• Chemotherapy drugs by themselves cannot differentiate between rapidly
dividing cancer cells and rapidly dividing healthy cells
• By implementing insulin in conjunction with chemotherapy drugs, the
cancer cells are highlighted as being different based on receptor
concentration and are promoted to grow more rapidly
• Cancer cells attacked more specifically

13. delta-9 desaturase
PLASMA MEMBRANE LESS
PERMEABLE
PLASMA MEMBRANE MORE
PERMEABLE
CHEMOTHERAPEUTIC DRUGS
ENTER MORE EASILY
STEARIC ACID
OLEIC ACID
INSULIN
TRISTEARIN TRIOLEIN
Increase in cell membrane permeability
+

14. GLYCODELIN
• Endocrine-regulated glycoprotein that has significant effects on
immune cells, apoptosis, reproduction, cell adhesion,
differentiation and cancer
• Growth restrictionof malignant cells
• Decreased expression of oncogenes
• Increasedexpression of tumour suppressor genes
• Morphological reversion of the malignant phenotype
• In the oviduct, glycodelin synthesis is stimulated by estrogen and
progesterone

15. Glycodelin transfected human MCF-7 breast cancer cells show
morphologic changes towards the normal phenotype in
different growth substrata

17. • Cancer originating from breast tissue,
most commonly from the inner lining
of milk ducts or the lobules that
supply the ducts with milk
• 100 times more common in women
than in men, although males tend to
have poorer outcomes due to delays
in diagnosis
• Some breast cancers are sensitive to
hormones such as estrogen and/or
progesterone, which makes it
possible to treat them by blocking
the effects of these hormones in the
target tissues
• Breast cancers without hormone
receptors, or which have spread to
the lymph nodes in the armpits, or
which express certain genetic
characteristics, are higher-risk

25. DEVELOPING TUMOR

27. Androgen-receptor signaling in prostate
cancer
• Hormone-dependent
androgen signaling takes
place through
dihydrotestosterone
stimulation of the androgen
receptor
• These culminate in
androgen-receptor signaling,
or alternate pathways that
lead to cell proliferation,
migration and survival

29. Hormonal effects of cows' milk on
human health
Harvard Club, Boston, October 24, 2006
Cows' milk contains estrogens and progesterone in large
quantities
The most abundant hormone in milk is estrone sulfate.
Converted into estrone or estradiol once within the body
Estrone sulfate is marketed as premarin(“pregnant mare”),
widely used in HRT
Commercial cow’s milk has uterotrophic activity on the uteri
of young ovariectomized and immmature rats( International
Journal of Cancer 118,2363-65,2006)
Combination of cheese and milk as the factor contributing
most to the incidence of testis and prostrate cancer
Commercial low fat milk promotes the development of
DBMA(7,12-dimethylbenzanthracene) induced mammary
tumors in rats

30. ADRENAL CANCER
• One of several benign and malignant
neoplasms of the adrenal gland, several of
which are notable for their tendency to
overproduce endocrine hormones
• Adrenal cortex- Adrenocortical Adenoma &
Adrenocortical Carcinoma
• Adrenocortical adenomas are benign tumor
& extremely common. Encapsulated, well-
circumscribed, solitary tumors with solid,
homogeneous yellow-cut surface
• Adrenocortical carcinoma (ACC) is a rare,
highly aggressive cancer. ACC's may be
"functional", producing steroid hormones
and consequent endocrine dysfunction

31. •Tumors of adrenal medulla-
Neuroblastoma &
Pheochromocytoma
•Neuroblastoma is an
aggressive cancer of
immature neuroblastic cells
and is one of the most
common pediatric cancers
•Pheochromocytoma is a
neoplasm composed of cells
similar to the chromaffin cells
of the mature adrenal
medulla
NEUROBLASTOMA
PHEOCHROMOCYTOMA

32. COLORECTAL CANCER
• Colon cancer or large bowel cancer or
"CRC“
• Cancerous growths in the colon,
rectum and appendix
• Starts with a mutation to the Wnt
signaling pathway
• Little evidence of an influence of
endogenous hormones on the risk of
colorectal cancer
• In contrast, there is evidence that
exogenous estrogens such as HRT,
tamoxifen, or oral contraceptives are
associated with colorectal tumors

33. Neuroendocrine tumor
• Gastro-entero-pancreatic or
gastroenteropancreatic neuroendocrine tumors
(GEP-NETs)
• Cancers of the interface between the endocrine
system and the nervous system
• Vast majority of GEP-NETs fall into two nearly
distinct categories: carcinoids and pancreatic
endocrine tumors (PETs)

34.  slow growing unlike other cancer cells
classified, depending on the point of origin, as foregut, midgut
and hind gut
may produce serotonin , a biogenic amine that causes a specific
set of symptoms including
CARCINOIDS
flushing
diarrhea or increase in number of bowel movements
weight loss
weight gain
congestive heart failure (CHF)
asthma
acromegaly

35. Pancreatic endocrine tumors
• Originate generally in the
islets of Langerhans within
the pancreas though they
may originate outside of the
pancreas too
• Mostly hormone secretory
tumors- Insulinoma,
gastrinoma, glucagonoma

36. The Hormone Foundation
• Established in 1997 by The Endocrine Society as its public
education affiliate
• Serves as a resource for physicians, patients, and the public by
promoting the prevention, treatment and cure of hormone-
related conditions through outreach and education
• Addresses endocrine conditions such as: Diabetes
Breast Cancer
Thyroid Disorders
Growth Disorders
Hormone Abuse
Obesity
Menopause
Osteoporosis
Pituitary Disorders
Low Testosterone
Metabolic Syndrome
Adrenal Disorders

37. DO’S
EAT HEALTHY…THINK
HEALTHY…LIVE HEALTHY

38. DON’TS !!!

39. SUMMING UP…….
 Genetic and non genetic factors
 IGF signaling pathway
 Action of steroid hormones
 Hormone therapy
 Hormone replacement therapy
 Insulin Potentiation Therapy
 Glycodelin
 Breast cancer
 Prostrate cancer
 Hormonal effects of cow’s milk
 Adrenal cancer
 Colorectal cancer
 Neuroendocrine tumors
 Hormone foundation
 Do’s and don’ts