HEYL as a therapeutic target and a diagnostic marker for neoplasia and uses therefor
The invention generally features compositions and methods that are useful for treating or diagnosing a neoplasia, in particular breast neoplasia. The invention is based in part on the observation that the basic helix loop helix transcription factor HEYL was found to be overexpressed in breast cancer cells. Accordingly, the invention provides therapeutic compositions and methods for altering the levels and expression of HEYL of the invention, thereby treating a neoplasia, as well as compositions and methods for diagnosing a neoplasia.
1. A method of diagnosing and treating a subject having breast cancer, comprising:
obtaining a sample of breast cancer epithelial cells from the subject;
preparing cDNA from the breast cancer epithelial cells sample;
contacting the cDNA with amplifying PCR primers comprising SEQ ID NOs: 2 and 3;
performing real time PCR, thereby forming an amplicon;
comparing the rate of formation of the amplicon in the breast cancer epithelial cells cDNA sample to an appropriate control cDNA sample or to a reference level;
diagnosing, based upon an increased rate of amplicon formation in the breast cancer epithelial cells cDNA sample, that the subject has breast cancer suitable for treatment with an agent that inhibits HEYL transcription or activity; and
administering an effective amount of the agent to the subject, thereby treating the diagnosed breast cancer.
2. A method of diagnosing and treating a subject having breast cancer, comprising:
obtaining a sample of breast cancer epithelial cells from the subject;
contacting the breast cancer epithelial cells sample with an antibody that specifically binds SEQ ID NO: 1, thereby forming an antibody-HEYL polypeptide complex;
detecting the antibody-HEYL polypeptide complex;
comparing the level of antibody-HEYL polypeptide complex in the breast cancer epithelial cells sample to an appropriate control or to a reference level;
diagnosing, based upon an increased level of antibody-HEYL polypeptide complex in the breast cancer epithelial cells sample, that the subject has breast cancer suitable for treatment with an agent that inhibits HEYL transcription or activity; and
administering an effective amount of the agent to the subject, thereby treating the diagnosed breast cancer.
3. The method of claim 1 , further comprising detecting a decrease in the nucleic acid or polypeptide level of Smad3 or a fragment thereof, or any combination thereof in the sample.
4. The method of claim 1 , further comprising detecting a decrease in TGF-beta activity, or any combination thereof in the sample.
5. A method of increasing or decreasing the administration of a treatment of a subject diagnosed as having breast cancer, comprising:
obtaining a sample of breast cancer epithelial cells from the subject;
preparing cDNA from the breast cancer epithelial cells sample;
preparing cDNA from the breast cancer epithelial cells sample;
contacting the cDNA with amplifying PCR primers comprising SEQ ID NOs: 2 and 3;
performing real time PCR, thereby forming an amplicon;
comparing the rate of formation of the amplicon in the breast cancer epithelial cells cDNA sample to an appropriate control cDNA sample or to a reference level;
administering an increased dosage of an agent that inhibits HEYL transcription or activity if the rate of formation of the amplicon in the breast cancer epithelial cells cDNA sample is greater than in the appropriate control cDNA sample or the reference level or administering a decreased dosage of an agent that inhibits HEYL transcription or activity if the rate of formation of the amplicon in the breast cancer epithelial cells cDNA sample is less than in the appropriate control cDNA sample or the reference level or administering the same dosage of an agent that inhibits HEYL transcription or activity if the rate of formation of the amplicon in the breast cancer epithelial cells cDNA sample is the same as in the appropriate control cDNA sample or the reference level.
6. The method of claim 1 , wherein the agent is selected from the group consisting of a HEYL inhibitor, a Notch inhibitor, and a Smad3 inhibitor.