TY - JOUR
T1 - Induction of apoptosis by EGF receptor in rat mammary adenocarcinoma cells coincides with enhanced spontaneous tumour metastasis
AU - Kaufmann, Andreas M.
AU - Lichtner, Rosemarie B.
AU - Schirrmacher, Volker
AU - Khazaie, Khashayarsha
PY - 1996
Y1 - 1996
N2 - The low metastatic MTC (13762NF) rat mammary adenocarcinoma cell line is devoid of epidermal growth factor receptor (EGFR). To test for a link between expression of EGFR and the ability of tumour cells to metastasise from their orthotopic site (spontaneous metastasis), stable subclones of this line (S+) that had been retrovirally transduced to express an ectopic full length HER1 were established and characterised. Proliferation, survival, and response to TGF-α were investigated and related to the tumorigenic growth and metastatic properties of the cells. S+ clones responded in vitro to ligand stimulation by growth inhibition and apoptosis. Upon orthotopic inoculation into the mammary fat pad of nude (nu/nu) mice, S+ clones showed retarded growth and apoptosed in situ, while MTC cells or neo(R) control cells showed no signs of apoptosis. Yet, S+ cells exhibited more spontaneous metastasis than the MTC parental cells or neo(R) control cells. Spontaneous metastasis requires cellular detachment (primary site) as well as attachment (secondary site) and growth in target organs. Neither the HER1 mediated increased ECM adhesion nor its negative effect on growth potential explains the observed effect. This is the first direct demonstration of the potential of EGFR to promote spontaneous metastasis of mammary adenocarcinoma cells from their orthotopic site.
AB - The low metastatic MTC (13762NF) rat mammary adenocarcinoma cell line is devoid of epidermal growth factor receptor (EGFR). To test for a link between expression of EGFR and the ability of tumour cells to metastasise from their orthotopic site (spontaneous metastasis), stable subclones of this line (S+) that had been retrovirally transduced to express an ectopic full length HER1 were established and characterised. Proliferation, survival, and response to TGF-α were investigated and related to the tumorigenic growth and metastatic properties of the cells. S+ clones responded in vitro to ligand stimulation by growth inhibition and apoptosis. Upon orthotopic inoculation into the mammary fat pad of nude (nu/nu) mice, S+ clones showed retarded growth and apoptosed in situ, while MTC cells or neo(R) control cells showed no signs of apoptosis. Yet, S+ cells exhibited more spontaneous metastasis than the MTC parental cells or neo(R) control cells. Spontaneous metastasis requires cellular detachment (primary site) as well as attachment (secondary site) and growth in target organs. Neither the HER1 mediated increased ECM adhesion nor its negative effect on growth potential explains the observed effect. This is the first direct demonstration of the potential of EGFR to promote spontaneous metastasis of mammary adenocarcinoma cells from their orthotopic site.
KW - Apoptosis
KW - EGF receptor
KW - Mammary carcinoma
KW - Metastasis
KW - Proliferation
KW - Retroviral gene transfer
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M3 - Article
C2 - 8957076
AN - SCOPUS:0030445323
SN - 0950-9232
VL - 13
SP - 2349
EP - 2358
JO - Oncogene
JF - Oncogene
IS - 11
ER -