Carcinogenesis, Vol 18, 23-29, Copyright © 1997 by Oxford University Press
C Luparello, MA Birch, JA Gallagher and WJ Burtis
It has been previously reported that 8701-BC cells, derived from a primary
carcinoma of the breast, constitutively express parathyroid hormone
(PTH)-related peptide (PTHrP) and PTH/PTHrP receptor (PTH/PTHrP- R) genes,
that N-terminal, mid-regional and C-terminal immunoreactive PTHrP can be
found in cell conditioned medium and, furthermore, that exogenously added
PTHrP (1-34), (67-86) and, to a minor extent, (107- 139) are anti-mitogenic
but promote Matrigel invasion by this cell line. It has also been reported
that PTHrP gene expression is selectively switched on in those 8701-BC
clonal lines endowed with a higher proliferation rate and invasive ability
in vitro. Here we have first examined the presence of PTH/PTHrP-R
transcript in the different 8701-BC clones by PCR and Southern blot
analysis. Second, we have studied the growth and invasive response in vitro
to PTHrP fragments by some of these clones, i.e. BC-3A, BC-61 and BC-66,
selected on the basis of their lower (BC-3A) or higher (BC-1 and BC-66)
Matrigel invasion ability and their expression of PTHrP (positive for BC-61
and BC-66) and PTH/PTHrP-R (positive for BC-61). Our data show the
existence of clonal heterogeneity for PTH/PTHrP-R mRNA and for the
proliferative and invasive responses elicited by treatment with diverse
PTHrP fragments. In particular: (i) the sensitivity to PTHrP (1-34) is
restricted due to the uneven expression of PTH/PTHrP-R; (ii) BC-3A cells
(the less 'aggressive' clone) are resistant to the anti-mitogenic effect of
the PTHrP domains and, most noticeably, exhibit a growth- potentiating
response to PTHrP (67-86) opposite to that found for both the parental
8701-BC cells and the two other clones; (iii) all PTHrP fragments tested
induced the expression of a growth-restraining and invasion-promoting
phenotype by BC-61 cells (one of the more 'aggressive' clones). Present
data in vitro support the hypothesis that in vivo PTHrP may be a key
element in local control of the invasive process during breast carcinoma
development and that its role may be, in turn, dependent upon the
biological characteristics and the level of malignancy of the target cells
within the multiclonal population of a primary tumour.
ARTICLES
Clonal heterogeneity of the growth and invasive response of a human breast carcinoma cell line to parathyroid hormone-related peptide fragments
Dipartimento di Biologia Cellulare e dello Sviluppo and Centro di Oncobiologia Sperimentale, Universita di Palermo, Italy.
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