# HUMAN BREAST SUSCEPTIBILITY TO TRANSFORMATION

> **NIH NIH R01** · FOX CHASE CANCER CENTER · 1991 · $268,490

## Abstract

Although environmental and chemical carcinogens are considered to
be important in the causation of human cancer, and polycyclic
hydrocarbons, nitrosoamides, aromatic amine derivatives and
nitroquinolines induce breast cancer in experimental animals, they
have not been proven to be carcinogenic for human breast epithelial
cells (HBEC).  Assessment of the role of chemical carcinogens in
human breast cancer requires the understanding of the mechanisms
by which normal cells become malignant and the availability of a
reproducible, quantitative system for transforming HBEC by exposure
to carcinogens.  In vitro treatment of HBEC with the chemical
carcinogens DMBA and NMU induces phenotypic changes, such as
anchorage independent growth and multinucleation, which are
modulated by the degree of gland development and pregnancy history.
Despite these advances, neither our group nor other investigators
have, as yet, successfully developed a reproducible system for the
complete transformation of HBEC into malignant cells with chemical
carcinogens.  This could be due to inadequacy of the models
utilized for HBEC transformation, to the fact that chemical
carcinogentreated cells expressing in vitro phenotypic changes of
cell transformation require an adequate heterologous system for
expression of the malignant phenotype, or that genotoxic chemical
carcinogens require an inherently susceptible target cell.  In
order to determine which factor(s) is/are responsible for the
modulation of the susceptibility of HBEC to malignant
transformation, we propose:  a) to use culture conditions that
maintain cells for long periods of time without terminal
differentiation or senescence, and that permit identification of
the transformed phenotype; b) to identify the phenotypes that
indicate early and late events of cell transformation,
characterizing each of the multisteps involved in carcinogenesis;
c) to determine whether cells exhibiting phenotypic markers of cell
transformation in vitro express in a heterologous host definitive
malignant phenotypes such as tumorigenicity, and d) to uncover
which common and constant features affecting the susceptibility of
the mammary gland to carcinogenesis are exhibited by the
heterogeneous human population, and whether those features are a
function of age or reproductive history.  The answer to these
questions will have immediate application to the development of
control measures for protecting the human breast from neoplastic
transformation.

## Key facts

- **NIH application ID:** 3177391
- **Project number:** 7R01CA038921-07
- **Recipient organization:** FOX CHASE CANCER CENTER
- **Principal Investigator:** JOSE RUSSO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $268,490
- **Award type:** 7
- **Project period:** 1984-12-01 → 1993-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177391

## Citation

> US National Institutes of Health, RePORTER application 3177391, HUMAN BREAST SUSCEPTIBILITY TO TRANSFORMATION (7R01CA038921-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177391. Licensed CC0.

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