the roles of niacin and calcium-sensing receptor expression in breast cancer malignancy and...

8/10/2019 The Roles of Niacin and Calcium-Sensing Receptor Expression in Breast Cancer Malignancy and Prognosis

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The Roles of Niacin andCalcium-Sensing ReceptorExpression in Breast Cancer

Malignancy and Prognosis

Max Rippe

Kala KielbasaAnthony Zamora

Jamie Hardybala

Orchid Haghighi


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Roadmap

Intro to Breast Cancer

Niacin Actiates !"#RMediated $ignaling

Methods Res%lts

Calci%m&sensing Receptor Methods

Res%lts

Releance o' Niacin andCalci%m in Breast Cancer

(%estions


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Introd%ction Breast cancer is the most common

cancer in )omen no matter the race

Approximately *+,-,,, )omen and*-+., men are diagnosed )ith breastcancer in the /0$0

Approximately 1,-,,, )omen and1+, men die 'rom breast cancer in the/0$0


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Ris2 3actors

4i''erent cancers hae characteristicris2 'actors

$ome can be controlled Haing children

Oral contracepties

Breast 'eeding

Alcohol cons%mption

Oer)eight5Obesity

"hysical actiity


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Ho)eer-

Many cannot be !ender

Ageing

!enetic M%tation BRCA65* 7breast cancer s%sceptibility

protein8

Constit%tie 4NA repair proteins

4amaged BRCA65* leaes cell%lnerable

Race


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9reatment

!eneral 9ypes o' 9reatment $%rgery

Radiation 9herapy Chemotherapy

Hormone 9herapy

9argeted 9herapy


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#''ectieness

4epends on 2ind o' breast cancer andextent o' gro)th and i' it has spread

3ie year s%rial rate )hen ca%ght early

I' ca%ght late the rate decreases by 6:; Ris2 increases )ith m%tations o' BRCA 65*

gene


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Niacin activates the protein-coupled estrogen receptor !PER"-mediated signaling

$antolla- M0 30- 4e 3rancesco- #0 M0-


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Introd%ction ! protein&co%pled estrogen receptor 7!"#R8

Inoled in cancer progression

>#R&positie? breast cancer #strogen dependence


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Introd%ction

9his st%dy aimed to determineAgonist stat%s o' niacin

#''ect o' binding on malignancy "roli'eration

Migration

Angiogenesis


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Methods and Materials

"roli'eration (%antitatie "roli'eration Assay

*1&)ell plates

$2BR+ breast cancer cells and Cancer&Associated3ibroblasts 7CA3s8 !"#R&positie

3or each cell type@60 shRNA nicotinic acid or nicotinamide

*0 sh!"#R nicotinic acid or nicotinamide !"#R >silencing?

+0 shRNA ehicle

10 sh!"#R ehicle

Cells co%nted by Co%ntess A%tomated Cell Co%nter

NOTE: Nicotinic acid and nicotinamide are separate treatment groups.


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Methods and Materials

Cell Migration Assay Boyden chambers

60 shRNA nicotinic

acid or nicotinamide*0 sh!"#R nicotinic

acid or nicotinamide

+0 shRNA ehicle

10 sh!"#R ehicle

Cells at bottom 'ixedand co%nted

http://en.wikipedia.org/wiki/Chemotaxis_assay

NOTE: Nicotinic acid and nicotinamide are separate treatment groups.


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Res%lts & "roli'eration

"icotinic acid and nicotinamide increased 'roliferation in both cell

t'es

SkBr3: sh!"# + "#"*,--. growth of /01r,s (' 2 -3-4)

CAFs: sh!"# + "#"*54-. growth of C#s (' 2 -3-4)

G$E! silencing

6nsignificant growth with "#7 "*7 or vehicle

Vehicle + sh!"#

6nsignificant growth


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Res%lts & Migration

"icotinic acid and nicotinamde increased migration in both cell

t'es

SkBr3: sh!"# + "#"*5--. migration

CAFs: sh!"# + "#"*

,4-%,8-. migration G$E! silencing

6nsignificant migration with "#7 "*7 or vehicle

Vehicle + sh!"#

6nsignificant growth


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Res%lts #ndothelial 9%be 3ormation

"icotinic acid increased endothelial tube formation

HUVECs:

sh!"# + CTG + "#584. more tubes 'er well

than vehicle

sh!"# + CTG + "#

,5-. more total tubelength 'er well than vehicle

sh!"# + CTG + "#,84. more branch 'oints

'er well than vehicle

G$E! silencing & insignificant growth

CTG silencing & insignificant growth


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4isc%ssion

6m'lications

"iacin can mediate biological functions

through rece'tors other than 0nownniacin rece'tors (e3g3 G!9-#)

Thera'eutic 'otential

;ecreased niacin inta0e in breast

cancer 'atients'ression: cause or effect

the roles of niacin and calcium-sensing receptor expression in breast cancer malignancy and...

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