BIOCHEMICAL

Vol. 89, No. 1, 1979 July 12, 1979

AND BIOPHYSICAL

RESEARCH COMMUNICATIONS Pages

175-180

NERVE GROWTH FACTOR-INDUCED REDUCTION IN EPIDERMAL GROWTH FACTOR RESPONSIVENESS AND AN ASPECT OF CELL DIFFERENTIATION EPIDERMAL GROWTH FACTOR RECEPTORS IN PC12 CELLS: Kenneth

and Gordon

Guroff

Section on Intermediary Metabolism Laboratory of Developmental Neurobiology Institute of Child Health and Human Development National Institutes of Health Bethesda, MD 20205

National

Received

R. Huff

May

29,1979 Summary

The rat pheochromocytoma clone PC12 responds to nerve growth factor through the expression of a number of differentiated neuronal properties. One of the most rapid changes is a large, transient increase in the activity of ornithine decarboxylase. These cells also show an increase in ornithine decarboxylase activity in response to the mitogen, epidermal growth factor, but do not respond morphologically as they do to nerve growth factor. Specific, high-affinity epidermal growth factor receptors are present on the cells. When the cells are differentiated with nerve growth factor, the response to epidermal growth factor is markedly diminished and there is a marked reduction in the binding of epidermal growth factor to the cells. Introduction The rat tumor

cell

pheochromocytoma line

development

(1).

growth

factor

NGF, but

This

Certain

(2).

types

than

trophic

responses

(ODC).

NGF-responsive in cellular Abbreviations:

systems

in many systems

activity

cells anabolism.

of

is the

respond

increase

superior

The effect

to nerve

have which

marker

EGF on ODC activity

NGF, nerve growth factor; ornithine decarboxylase.

EGF, epidermal

known

17.5

for

of ornithine

for

range

(7),

including

impending

growth

NGF (6), decarboxy-

in PC12 cells

0006-291 Copyright AU rights

to

demonstrated

in many systems (B),

epidermal

in a broader

are also

ganglia

factor

similarities

recently

activity

growth

hormone,

responses

in the

cervical of

of morphological,

to a related

and elicits

adrenergic

of neuronal

and biological

to EGF (4,5),

a nuclear

as a model

in response

We and others

is a several-fold

crest-derived

many aspects

has some biochemical

does NGF (3).

This

recently

demonstrates

of PC12 cells

and among which

a neural

differentiation

which

is mitogenic

of cell

lase

cell

non-neural

(EGF),

PC12 is

has been studied