# ANALYSIS OF PROGRESSION OF THE TRANSFORMED PHENOTYPE

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1988 · $187,309

## Abstract

The objectives are to analyze the cellular, biochemical and genetic changes
associated with progression of the transformed phenotype in cloned
populations of type 5 adenovirus (Ad5) transformed rodent cells and in
lectin resistant ("glycosylation mutant") human melanoma cells stably
expressing an increased metastatic potential in vivo.  Based on experiments
indicating that the progression phenotype in Ad5-transformed rat embryo
cells in reversible and no systematic changes occur in either the
transcription of Ad5-early genes or the levels of Ad5-transforming proteins
in cells displaying various stages of progression, experiments will focus
on determining the role of cellular genes (including oncogenes) in
regulating the progression phenotype.  Several approaches will be used to
study this process, including:  (a) somatic cell hybridization between
cells displaying a progressed phenotype and normal, unprogressed or
subclones of progressed cells treated with azacytidine and stably
displaying an unprogressed phenotype; (b) DNA transfection experiments to
determine if various oncogene products localized in the cytoplasm can
complement the nuclear localized Ad5 E1a gene products resulting in
progression; (c) high resolution 2-D protein gel electrophoresis to
investigate the spectrum of protein changes associated with the acquisition
and the reversion of the progressed phenotype; and (d) molecular cloning
techniques to identify and clone potential suppressor genes which when
expressed prevent progression of the transformed phenotype.

Using the human melanoma model system, investigations will be conducted to
determine the potential mechanism by which metastatic melanoma cells
display the progressed phenotype.  These studies will include:  (a)
evaluating the potential role of oncogene activation in determining the
metastatic phenotype; (b) identifying specific protein changes by 2-D
protein gel electrophoresis which occur concomitant with expression of the
metastatic phenotype; and (c) DNA-transfection studies to transfer and
identify human metastasis genes.

The present investigations should permit a better molecular definition of
the process of progression of the transformed phenotype in both rodent and
human cells.  In addition, since the carcinogenic process is often a
multistep process the present studies should also provide insights into the
molecular basis for carcinogenesis and potential mechanism for suppressing
oncogenic transformation.

## Key facts

- **NIH application ID:** 3173267
- **Project number:** 5R01CA035675-05
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** PAUL B FISHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $187,309
- **Award type:** 5
- **Project period:** 1984-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173267

## Citation

> US National Institutes of Health, RePORTER application 3173267, ANALYSIS OF PROGRESSION OF THE TRANSFORMED PHENOTYPE (5R01CA035675-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173267. Licensed CC0.

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