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Physiology of Disease > The role of VHL in Kidney Cancer > Flashcards

The role of VHL in Kidney Cancer Flashcards

1
Q

What are the two forms that VHL exists as?

A

VHL30
VHL19

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2
Q

What is VHL?

A

The substrate conferring component of the VHL-elongin B-elongin C (VBC) complex

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3
Q

What is the VBC complex?

A

Group of proteins that work together to form an E3 ubiquitin ligase (decorates HIF)

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4
Q

What is polyubiquintated HIF degraded by?

A

26S proteosome

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5
Q

What 5 problems can a tumour in your kidneys cause?

A

Blood in urine
Lump in kidney area
Painful spasms in kidney tubes or bladder
high temperatures & night sweats
Tiredness and weight loss

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6
Q

Which cancer is 85% of all kidney cancers?

A

Renal cell carcinoma

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7
Q

What is the most common form of RCC?

A

Clear cell renal cell carcinoma

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8
Q

What do people with VHL disease also get?

A

ccRCC

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9
Q

What is lost in almost all sporadic ccRCC cases?

A

VHL is lost or mutated

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10
Q

What is pseudohypoxia?

A

Process wherein cells express hypoxia associated proteins regardless of oxygen status

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11
Q

What is the HRE sequence?

A

5’-RCGTG-3’

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12
Q

Out of 1,114,925 RCGTG sites how many are available to HIF-1a and 2a?

A

0.04% and 0.05% respectively

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13
Q

In ccRCC what is HIF-2alpha’s role?

A

Tumour growth

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14
Q

What are 2 possible roles for HIF-1alpha?

A

promotes early stages of tumourigenesis
HIF1 is a tumour suppressor whereas HIF2a is an oncogene

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15
Q

What 5 genes does HIF2a promote?

A

VEGF
Cyclin D1 (proliferation)
TGF alpha (proliferation)
GAL3ST1 (metastasis)
Plin2 (deregulating cellular metabolism)

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16
Q

What part of the cell cycle is mediated by Cyclin D1?

A

G1/S transition

17
Q

What does increased PLIN2 cause?

A

Increased lipid droplets

18
Q

What does GAL3ST1 increase?

A

Cancer cell evasion of immune cells

19
Q

What is a HIF2a inhibitor?

A

Belzutifan

20
Q

What 3 types of cancers has belzutifan been approved for?

A

patients with VHL disease that require therapy for RCC, CNS hemangioblastomas or pancreatic neuroendocrine tumours

21
Q
A

Physiology of Disease (15 decks)

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